Table of SynGAP1 Isoform α2 (UniProt Q96PV0-1) Missense Variants.

c.dna	Variant	SGM Consensus	Domain and Structure information: based on WT protein												Annotated databases						Deep learning-based pathogenicity predictions					Folding stability-based pathogenicity predictions									Sequence/structure-based pathogenicity predictions														Phase Separation			Evolutionary/physical properties				Molecular Dynamics-based analysis															DOI
			Domain	IUPred2		ANCHOR2		AlphaFold		MobiDB	PhosphoSitePlus				ClinVar			gnomAD			ESM1b		AlphaMissense			FoldX			Rosetta		Foldetta		PremPS		REVEL		PROVEAN		PolyPhen-2 HumDiv		PolyPhen-2 HumVar		FATHMM		SIFT				PSMutPred			PAM		Physical		SASA		Normalized B-factor backbone		Normalized B-factor sidechain		SynGAP Structural Annotation
				Score	Prediction	Score	Prediction	pLDDT	disorder	disorder	LTP	HTP	KL	PTM	Clinical Status	Review	Subm.	ID	Allele count	Allele freq.	LLR score	Prediction	Pathogenicity	Class	Optimized	Average ΔΔG	Prediction	StdDev	ΔΔG	Prediction	ΔΔG	Prediction	ΔΔG	Prediction	Score	Prediction	Score	Prediction	pph2_prob	Prediction	pph2_prob	Prediction	Nervous System Score	Prediction	Prediction	Status	Conservation	Sequences	IP RF	SP RF	Prediction	PAM250	PAM120	Hydropathy Δ	MW Δ	Average	Δ	Δ	StdDev	Δ	StdDev	Secondary	Tertiary bonds	Inside out	GAP-Ras interface	At membrane	No effect	MD Alert	Verdict	Description
c.829A>G	K277E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K277E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, and Foldetta. Tools that agree on a pathogenic effect include SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. No predictions are missing or inconclusive. Overall, the majority of tools (10/13) predict pathogenicity, whereas only three predict benign. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.061840	Structured	0.321811	Uncertain	0.649	0.247	0.250											-14.886	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	-0.14	Likely Benign	0.1	0.18	Likely Benign	0.02	Likely Benign	0.51	Ambiguous	0.694	Likely Pathogenic	-3.68	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.85	Pathogenic	0.01	Affected			0.3462	0.0492		0	1	0.4	0.94
c.830A>G	K277R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K277R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Foldetta, premPS, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and FATHMM. Rosetta gives an uncertain result. High‑accuracy methods give a benign prediction from AlphaMissense‑Optimized and from Foldetta; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it is a 2‑vs‑2 split. Overall, the majority of evidence (7 benign vs. 5 pathogenic) supports a benign classification. This consensus does not contradict any ClinVar annotation, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.061840	Structured	0.321811	Uncertain	0.649	0.247	0.250											-6.652	Likely Benign	0.156	Likely Benign	Likely Benign	-0.01	Likely Benign	0.1	0.53	Ambiguous	0.26	Likely Benign	0.06	Likely Benign	0.518	Likely Pathogenic	-2.76	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.83	Pathogenic	0.06	Tolerated			0.4232	0.0678		3	2	-0.6	28.01
c.832A>G	K278E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K278E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, and SIFT, all of which score the substitution as tolerated. In contrast, a majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic verdict. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, predicts a benign effect. premPS is inconclusive and therefore not considered evidence. High‑accuracy assessments therefore show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as pathogenic, and Foldetta as benign. Overall, the preponderance of evidence from multiple independent predictors indicates that K278E is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.120615	Structured	0.310130	Uncertain	0.748	0.253	0.125											-14.047	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.40	Likely Benign	0.1	0.39	Likely Benign	0.40	Likely Benign	0.68	Ambiguous	0.463	Likely Benign	-3.64	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.76	Pathogenic	0.06	Tolerated			0.3189	0.0492		0	1	0.4	0.94
c.833A>G	K278R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K278R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it yields an equal split of benign and pathogenic calls. Overall, the majority of evidence points to a benign impact. Thus, the variant is most likely benign, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.120615	Structured	0.310130	Uncertain	0.748	0.253	0.125											-5.313	Likely Benign	0.216	Likely Benign	Likely Benign	-0.05	Likely Benign	0.0	0.18	Likely Benign	0.07	Likely Benign	0.13	Likely Benign	0.282	Likely Benign	-2.66	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.73	Pathogenic	0.10	Tolerated			0.3926	0.0489		3	2	-0.6	28.01
c.847G>A	E283K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E283K is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL and FoldX, whereas the majority of algorithms predict it to be pathogenic: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Uncertain results come from Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.358602	Uncertain	0.950	0.249	0.000											-14.350	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.30	Likely Benign	0.1	0.82	Ambiguous	0.56	Ambiguous	0.62	Ambiguous	0.443	Likely Benign	-3.68	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.92	Pathogenic	0.01	Affected			0.2989	0.5714		0	1	-0.4	-0.94
c.848A>C	E283A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E283A is reported in gnomAD (ID 6‑33437753‑A‑C) but has no ClinVar entry. Functional prediction tools that agree on a deleterious effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, all labeling the change as pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. Predictions that are inconclusive or unavailable—FoldX, Rosetta, Foldetta, and premPS—do not provide evidence for or against pathogenicity. High‑accuracy assessments confirm the deleterious nature: AlphaMissense‑Optimized predicts pathogenic, SGM Consensus indicates Likely Pathogenic, while Foldetta remains uncertain. Taken together, the overwhelming majority of evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.358602	Uncertain	0.950	0.249	0.000								6-33437753-A-C	2	1.24e-6	-12.547	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	1.26	Ambiguous	0.1	1.19	Ambiguous	1.23	Ambiguous	0.53	Ambiguous	0.529	Likely Pathogenic	-5.52	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.67	Pathogenic	0.01	Affected	3.38	19	0.4104	0.5807		-1	0	5.3	-58.04
c.889A>G	K297E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K297E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate pathogenicity, while the SGM‑Consensus score is “Likely Pathogenic.” No tool in the dataset predicts a benign outcome; the only inconclusive result is FoldX, which is listed as “Uncertain” and is treated as unavailable. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the collective predictions, K297E is most likely pathogenic, and this conclusion does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.422041	Structured	0.272593	Uncertain	0.880	0.285	0.375											-10.143	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.99	Ambiguous	0.4	2.43	Destabilizing	2.21	Destabilizing	1.16	Destabilizing	0.507	Likely Pathogenic	-3.54	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.61	Pathogenic	0.02	Affected			0.4073	0.1547		0	1	0.4	0.94
c.890A>G	K297R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K297R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Foldetta, PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar) and FATHMM. Predictions that are uncertain or inconclusive are FoldX, Rosetta, premPS, and ESM1b. High‑accuracy methods give a consistent benign signal: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also resolves to benign; and Foldetta, a protein‑folding stability approach combining FoldX‑MD and Rosetta, predicts benign. Based on the aggregate of these predictions, the variant is most likely benign, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.422041	Structured	0.272593	Uncertain	0.880	0.285	0.375											-7.877	In-Between	0.314	Likely Benign	Likely Benign	-0.86	Ambiguous	0.3	0.67	Ambiguous	-0.10	Likely Benign	0.66	Ambiguous	0.257	Likely Benign	-2.36	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	1.66	Pathogenic	0.19	Tolerated			0.4828	0.1506		3	2	-0.6	28.01
c.901G>C	A301P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A301P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only two tools—polyPhen‑2 HumDiv and polyPhen‑2 HumVar—predict a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign; and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.429200	Structured	0.258424	Uncertain	0.647	0.272	0.375											-3.808	Likely Benign	0.085	Likely Benign	Likely Benign	-0.47	Likely Benign	0.1	-0.41	Likely Benign	-0.44	Likely Benign	0.40	Likely Benign	0.225	Likely Benign	-0.83	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	4.11	Benign	0.06	Tolerated			0.1907	0.5371		1	-1	-3.4	26.04
c.902C>A	A301D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A301D is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors shows a predominance of benign calls: REVEL, FoldX, premPS, PROVEAN, SIFT, and FATHMM all predict benign, whereas polyPhen‑2 (HumDiv and HumVar) and ESM1b predict pathogenic. Tools with uncertain outputs—Rosetta, Foldetta, and AlphaMissense‑Default—do not provide decisive evidence. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized classifies the variant as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also yields a benign verdict; Foldetta remains inconclusive. Taken together, the preponderance of evidence indicates that A301D is most likely benign, and this assessment does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.429200	Structured	0.258424	Uncertain	0.647	0.272	0.375											-10.276	Likely Pathogenic	0.488	Ambiguous	Likely Benign	-0.37	Likely Benign	0.2	-1.15	Ambiguous	-0.76	Ambiguous	0.23	Likely Benign	0.224	Likely Benign	-0.35	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	4.17	Benign	0.07	Tolerated			0.1599	0.1705		0	-2	-5.3	44.01
c.928G>A	E310K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E310K is listed in ClinVar with an uncertain significance (ID 981613) and is not reported in gnomAD. Functional prediction tools uniformly indicate a deleterious effect: SGM‑Consensus, REVEL, FoldX‑MD (uncertain), Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool predicts a benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is pathogenic. Consequently, the variant is most likely pathogenic according to the available predictions, which does not contradict the ClinVar uncertain status but suggests a pathogenic interpretation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.222385	Structured	0.346136	Uncertain	0.914	0.337	0.125					Conflicting		5				-14.601	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	1.97	Ambiguous	1.2	3.66	Destabilizing	2.82	Destabilizing	1.02	Destabilizing	0.764	Likely Pathogenic	-3.68	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	1.19	Pathogenic	0.01	Affected	3.38	19	0.2496	0.8453		0	1	-0.4	-0.94	213.4	58.0	0.1	0.0	0.2	0.1		X						Potentially Pathogenic	The carboxylate group of Glu310, located in an anti-parallel β sheet strand (res. Thr305-Asn315), is ideally positioned to interact with the side chain hydroxyl and backbone amide groups of Thr295 on a twisted anti-parallel β strand (res. Met289-Arg299). Because the carboxylate group can also interact with the GAP domain residues (e.g., Gln612, Tyr614), Glu310 plays a key role in maintaining the tertiary assembly between the C2 and GAP domains. In the variant simulations, the amino group of the Lys310 side chain hydrogen bonds with the GAP domain residues and forms a salt bridge with Glu613. Although no apparent negative effects are seen due to the residue swap, it is possible that the loss of hydrogen bonding with the hydroxyl group of the Thr295 side chain causes problems during folding, potentially compromising the twisting of the β sheet.
c.929A>C	E310A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E310A missense variant is not reported in ClinVar or gnomAD. Prediction tools largely converge on a pathogenic effect: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate pathogenicity, while premPS is the sole benign predictor. Uncertain calls come from FoldX, Rosetta, and Foldetta. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus labels it likely pathogenic, and Foldetta remains inconclusive. With the overwhelming majority of evidence pointing to deleterious impact and no ClinVar annotation to contradict, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.222385	Structured	0.346136	Uncertain	0.914	0.337	0.125											-13.878	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	1.65	Ambiguous	0.6	1.65	Ambiguous	1.65	Ambiguous	0.50	Likely Benign	0.850	Likely Pathogenic	-5.52	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.16	Pathogenic	0.01	Affected			0.3980	0.8097		0	-1	5.3	-58.04
c.937G>A	E313K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E313K is listed in ClinVar as Benign (ClinVar ID 3695040.0) and is not reported in gnomAD. Prediction tools that report a benign effect are absent; all available predictors that provide a definitive call classify the variant as pathogenic. These include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts Pathogenic, the SGM‑Consensus indicates Likely Pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) is Uncertain. Based on the overwhelming pathogenic predictions, the variant is most likely pathogenic, which contradicts its ClinVar benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.170161	Structured	0.366526	Uncertain	0.898	0.304	0.125					Likely Benign		1				-12.902	Likely Pathogenic	0.959	Likely Pathogenic	Likely Pathogenic	0.64	Ambiguous	0.6	1.40	Ambiguous	1.02	Ambiguous	0.75	Ambiguous	0.575	Likely Pathogenic	-3.31	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	1.90	Pathogenic	0.02	Affected			0.2540	0.7708		0	1	-0.4	-0.94
c.938A>C	E313A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E313A is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized, whereas the remaining pathogenic‑or‑likely‑pathogenic predictors are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Four tools (FoldX, Rosetta, Foldetta, premPS) returned uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic effect. Thus, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.170161	Structured	0.366526	Uncertain	0.898	0.304	0.125											-14.591	Likely Pathogenic	0.747	Likely Pathogenic	Likely Benign	1.07	Ambiguous	0.3	0.97	Ambiguous	1.02	Ambiguous	0.62	Ambiguous	0.680	Likely Pathogenic	-4.88	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.88	Pathogenic	0.02	Affected			0.3416	0.6743		0	-1	5.3	-58.04
c.943A>G	N315D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N315D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar) and FATHMM. The remaining tools (FoldX, premPS, AlphaMissense‑Default) are inconclusive. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign majority; and Foldetta predicts a benign stability change. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.118441	Structured	0.379740	Uncertain	0.862	0.253	0.125											-5.667	Likely Benign	0.536	Ambiguous	Likely Benign	1.27	Ambiguous	0.6	-0.30	Likely Benign	0.49	Likely Benign	0.88	Ambiguous	0.229	Likely Benign	-2.41	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	2.02	Pathogenic	0.45	Tolerated			0.1972	0.4488		2	1	0.0	0.98
c.944A>C	N315T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N315T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), and FATHMM. Two tools, premPS and ESM1b, return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of individual predictors (six benign vs. four pathogenic) and the Foldetta result support a benign classification, while the SGM Consensus suggests pathogenicity. Thus, the variant is most likely benign based on the preponderance of evidence, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.118441	Structured	0.379740	Uncertain	0.862	0.253	0.125											-7.071	In-Between	0.211	Likely Benign	Likely Benign	0.31	Likely Benign	0.1	-0.36	Likely Benign	-0.03	Likely Benign	0.62	Ambiguous	0.333	Likely Benign	-2.91	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.95	Pathogenic	0.53	Tolerated			0.1471	0.8068		0	0	2.8	-13.00
c.946A>G	N316D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N316D is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, Rosetta, SIFT, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is uncertain and therefore not considered evidence. Overall, seven of the evaluated tools predict pathogenicity versus four predicting benignity, indicating that the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar classification is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.118441	Structured	0.385187	Uncertain	0.817	0.246	0.125											-11.672	Likely Pathogenic	0.777	Likely Pathogenic	Likely Benign	1.18	Ambiguous	0.1	0.46	Likely Benign	0.82	Ambiguous	0.69	Ambiguous	0.293	Likely Benign	-3.20	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.76	Pathogenic	0.25	Tolerated			0.1978	0.4596		2	1	0.0	0.98
c.947A>C	N316T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N316T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and FATHMM. The remaining tools (AlphaMissense‑Default, ESM1b, Foldetta, premPS, Rosetta) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta also yields an uncertain stability change. Overall, the majority of available predictions lean toward pathogenicity, and this assessment does not contradict any ClinVar annotation (none is present). Thus, the variant is most likely pathogenic based on the current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.118441	Structured	0.385187	Uncertain	0.817	0.246	0.125											-7.538	In-Between	0.550	Ambiguous	Likely Benign	2.71	Destabilizing	0.2	1.27	Ambiguous	1.99	Ambiguous	0.57	Ambiguous	0.214	Likely Benign	-3.68	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.79	Pathogenic	0.08	Tolerated			0.1482	0.8474		0	0	2.8	-13.00
c.997A>G	K333E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K333E missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, and SIFT. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evidence points to a pathogenic impact for K333E. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.311707	Structured	0.330781	Uncertain	0.537	0.447	0.500											-14.059	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	-0.06	Likely Benign	0.2	0.30	Likely Benign	0.12	Likely Benign	0.89	Ambiguous	0.488	Likely Benign	-3.21	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.91	Pathogenic	0.09	Tolerated			0.3429	0.1039		0	1	0.4	0.94
c.998A>G	K333R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K333R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Consensus predictions from multiple in‑silico tools cluster into two groups: benign (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus “Likely Benign”) and pathogenic (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM). High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign”, and Foldetta (combining FoldX‑MD and Rosetta outputs) also indicates benign stability. No prediction or folding result is missing or inconclusive. Overall, the majority of evidence points to a benign effect for K333R, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.311707	Structured	0.330781	Uncertain	0.537	0.447	0.500											-4.897	Likely Benign	0.120	Likely Benign	Likely Benign	-0.23	Likely Benign	0.0	0.15	Likely Benign	-0.04	Likely Benign	0.33	Likely Benign	0.232	Likely Benign	-2.02	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	2.01	Pathogenic	0.14	Tolerated			0.4294	0.1134		3	2	-0.6	28.01
c.1028T>G	V343G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V343G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—classify the variant as pathogenic. AlphaMissense‑Optimized is uncertain, providing no definitive direction. High‑accuracy assessments further support pathogenicity: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Thus, the preponderance of evidence indicates that V343G is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.291804	Structured	0.383911	Uncertain	0.882	0.497	0.250											-11.332	Likely Pathogenic	0.926	Likely Pathogenic	Ambiguous	2.49	Destabilizing	0.1	4.40	Destabilizing	3.45	Destabilizing	1.68	Destabilizing	0.421	Likely Benign	-5.84	Deleterious	0.898	Possibly Damaging	0.996	Probably Damaging	1.60	Pathogenic	0.00	Affected			0.1982	0.3341		-1	-3	-4.6	-42.08
c.1045C>A	P349T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P349T is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and the SGM‑Consensus score (which is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools with inconclusive results are AlphaMissense‑Default, FoldX, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic, and Foldetta as uncertain. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists for this variant. Thus, the variant is most likely pathogenic based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.167087	Structured	0.348607	Uncertain	0.947	0.396	0.000											-9.736	Likely Pathogenic	0.420	Ambiguous	Likely Benign	1.37	Ambiguous	0.1	2.56	Destabilizing	1.97	Ambiguous	0.76	Ambiguous	0.246	Likely Benign	-6.12	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.57	Pathogenic	0.07	Tolerated			0.1615	0.6238		0	-1	0.9	3.99
c.1045C>T	P349S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P349S missense variant is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Predictions that are inconclusive or uncertain are FoldX, ESM1b, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of tools, including the high‑accuracy methods, predict a pathogenic effect. Thus, the variant is most likely pathogenic, which does not contradict its current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.167087	Structured	0.348607	Uncertain	0.947	0.396	0.000					Uncertain		1				-7.654	In-Between	0.217	Likely Benign	Likely Benign	1.92	Ambiguous	0.1	2.28	Destabilizing	2.10	Destabilizing	0.87	Ambiguous	0.277	Likely Benign	-6.13	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.66	Pathogenic	0.06	Tolerated	3.37	25	0.3771	0.5756		1	-1	0.8	-10.04	194.9	-18.1	-0.1	0.0	0.2	0.1	X						X	Potentially Pathogenic	The cyclic pyrrolidine side chain of Pro349, located at the end of an anti-parallel β sheet strand (res. Gly341-Pro349), allows the strand to end and make a tight turn before a short α helical section within a loop connecting to another β strand (res. Thr359-Pro364). In the variant simulations, the hydroxyl group of Ser349 forms a hydrogen bond with the backbone amide group of Ala351 in the short helical section. Conversely, the backbone amide group of Ser349 (absent in proline) does not form any intra-protein hydrogen bonds. However, the β strand end connects to the α helical section in a more stable and consistent manner compared to the WT. Although the residue swap does not cause major adverse effects on the protein structure in the simulations, it is possible that the tight turn at the β strand end could not be created during folding without the presence of proline.
c.1064G>C	G355A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 G355A missense change is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. FoldX and Foldetta are uncertain and therefore not counted as evidence. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic) and Foldetta is uncertain. Consequently, the overall prediction leans toward a benign effect, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.155435	Structured	0.388832	Uncertain	0.810	0.354	0.125											-5.431	Likely Benign	0.245	Likely Benign	Likely Benign	0.88	Ambiguous	0.6	0.46	Likely Benign	0.67	Ambiguous	0.49	Likely Benign	0.286	Likely Benign	-4.80	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.80	Pathogenic	0.03	Affected			0.4111	0.5045		1	0	2.2	14.03
c.1084T>A	W362R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W362R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify it as pathogenic. Benign predictions are absent; all evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—return pathogenic or likely pathogenic calls. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports pathogenic. Consequently, the variant is most likely pathogenic, with no conflict with ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.430310	Uncertain	0.957	0.552	0.125											-14.004	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	2.64	Destabilizing	0.3	3.90	Destabilizing	3.27	Destabilizing	1.10	Destabilizing	0.706	Likely Pathogenic	-12.87	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.28	Pathogenic	0.00	Affected	3.39	24	0.4811	0.0571		2	-3	-3.6	-30.03	287.5	-34.1	-0.2	0.1	-0.6	0.2	X			X			X	Potentially Pathogenic	The indole ring of Trp362, located on the surface of an anti-parallel β sheet (res. Thr359-Pro364) in the C2 domain, stacks with nearby residues (e.g., Arg401, Arg272). In the variant simulations, the guanidinium group of the introduced residue Arg362 forms a salt bridge with the carboxylate group of Glu273 and, like Trp362, stacks with other arginine residues (e.g., Arg401, Arg272). This residue is at both the C2-membrane interface and the C2-RasGTPase interface, so the residue swap could potentially affect both interactions. However, these phenomena cannot be addressed using solvent-only simulations. Notably, Arg272, which stacks with both the non-mutated Trp362 and the mutated Arg362, forms a salt bridge directly with Asp105 of Ras in the WT simulations. Therefore, the residue swap could affect the C2 domain stability, the SynGAP-membrane association, and the SynGAP-Ras association.	10.1016/j.ajhg.2020.11.011
c.1084T>C	W362R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W362R (ClinVar ID 41461.0) is listed as Pathogenic and is not reported in gnomAD. All available in silico predictors classify the variant as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments concur: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) reports Pathogenic. Thus, the variant is most likely pathogenic, and this prediction aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.430310	Uncertain	0.957	0.552	0.125					Pathogenic		2				-14.004	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	2.64	Destabilizing	0.3	3.90	Destabilizing	3.27	Destabilizing	1.10	Destabilizing	0.706	Likely Pathogenic	-12.87	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.28	Pathogenic	0.00	Affected	3.39	24	0.4811	0.0571		2	-3	-3.6	-30.03	287.5	-34.1	-0.2	0.1	-0.6	0.2	X			X			X	Potentially Pathogenic	The indole ring of Trp362, located on the surface of an anti-parallel β sheet (res. Thr359-Pro364) in the C2 domain, stacks with nearby residues (e.g., Arg401, Arg272). In the variant simulations, the guanidinium group of the introduced residue Arg362 forms a salt bridge with the carboxylate group of Glu273 and, like Trp362, stacks with other arginine residues (e.g., Arg401, Arg272). This residue is at both the C2-membrane interface and the C2-RasGTPase interface, so the residue swap could potentially affect both interactions. However, these phenomena cannot be addressed using solvent-only simulations. Notably, Arg272, which stacks with both the non-mutated Trp362 and the mutated Arg362, forms a salt bridge directly with Asp105 of Ras in the WT simulations. Therefore, the residue swap could affect the C2 domain stability, the SynGAP-membrane association, and the SynGAP-Ras association.	10.1016/j.ajhg.2020.11.011
c.1086G>C	W362C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W362C is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify it as pathogenic: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect, so the benign group is empty. High‑accuracy methods reinforce this assessment: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Consequently, the variant is most likely pathogenic based on the consensus of all predictions, and this conclusion does not contradict the ClinVar status, which simply lacks an entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.430310	Uncertain	0.957	0.552	0.125											-11.200	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.68	Destabilizing	0.1	4.06	Destabilizing	3.87	Destabilizing	1.00	Destabilizing	0.618	Likely Pathogenic	-11.95	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.24	Pathogenic	0.00	Affected			0.4158	0.1622		-8	-2	3.4	-83.07
c.1086G>T	W362C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W362C is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity uniformly classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic effect. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized indicates pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a pathogenic impact on protein stability. Based on the unanimous pathogenic predictions and the absence of any benign calls, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which simply lacks an entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.430310	Uncertain	0.957	0.552	0.125											-11.200	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.68	Destabilizing	0.1	4.06	Destabilizing	3.87	Destabilizing	1.00	Destabilizing	0.618	Likely Pathogenic	-11.95	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.24	Pathogenic	0.00	Affected			0.4158	0.1622		-8	-2	3.4	-83.07
c.1088A>G	Y363C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y363C is not reported in ClinVar (ClinVar ID: None) but is present in gnomAD (ID 6‑33437993‑A‑G). Prediction tools cluster into two groups: benign predictions come from REVEL and AlphaMissense‑Optimized, whereas the remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—indicate pathogenicity. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. With the majority of evidence pointing to deleterious effects and no ClinVar annotation to contradict, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.435392	Uncertain	0.954	0.586	0.125								6-33437993-A-G	1	7.13e-7	-9.059	Likely Pathogenic	0.721	Likely Pathogenic	Likely Benign	2.21	Destabilizing	0.1	3.96	Destabilizing	3.09	Destabilizing	2.05	Destabilizing	0.414	Likely Benign	-8.07	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.54	Pathogenic	0.00	Affected	3.39	24	0.3759	0.3463		-2	0	3.8	-60.04
c.1090C>A	P364T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P364T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 (HumDiv and HumVar), and FATHMM. Four tools (FoldX, Foldetta, premPS, ESM1b) return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evaluated tools (five benign versus four pathogenic) lean toward a benign classification, and this assessment does not contradict any ClinVar annotation because no ClinVar claim exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.390993	Structured	0.439474	Uncertain	0.942	0.590	0.250											-7.951	In-Between	0.230	Likely Benign	Likely Benign	1.18	Ambiguous	0.6	0.47	Likely Benign	0.83	Ambiguous	0.53	Ambiguous	0.342	Likely Benign	-5.60	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.60	Pathogenic	0.09	Tolerated			0.1660	0.5726		0	-1	0.9	3.99
c.1090C>T	P364S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P364S resides in the C2 domain. It is not reported in ClinVar and is present in gnomAD (ID 6‑33437995‑C‑T). Prediction tools that classify the variant as benign include REVEL, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM; the SGM‑Consensus score is also labeled Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Uncertain. No prediction or stability result is missing or inconclusive beyond the Uncertain labels. Based on the majority of evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.390993	Structured	0.439474	Uncertain	0.942	0.590	0.250								6-33437995-C-T	1	6.20e-7	-8.318	Likely Pathogenic	0.214	Likely Benign	Likely Benign	1.34	Ambiguous	0.3	0.68	Ambiguous	1.01	Ambiguous	0.83	Ambiguous	0.307	Likely Benign	-5.98	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.62	Pathogenic	0.05	Affected	3.39	20	0.3390	0.5512		-1	1	0.8	-10.04
c.1132G>C	G378R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G378R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from premPS, PROVEAN, and SIFT, while pathogenic predictions arise from REVEL, FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts benign, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also indicates pathogenicity. Overall, the preponderance of evidence points to a pathogenic impact for G378R. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.767246	Disordered	0.432858	Uncertain	0.341	0.915	0.625											-8.863	Likely Pathogenic	0.745	Likely Pathogenic	Likely Benign	12.27	Destabilizing	6.3	13.17	Destabilizing	12.72	Destabilizing	0.12	Likely Benign	0.653	Likely Pathogenic	-0.96	Neutral	1.000	Probably Damaging	0.996	Probably Damaging	1.32	Pathogenic	0.06	Tolerated			0.1343	0.4356		-3	-2	-4.1	99.14
c.1132G>T	G378C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G378C is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include premPS, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of tools (8/12) predict pathogenicity, and the high‑accuracy consensus leans toward benign only for AlphaMissense‑Optimized and SGM Consensus, while Foldetta indicates instability. Thus, the variant is most likely pathogenic based on the preponderance of evidence, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.767246	Disordered	0.432858	Uncertain	0.341	0.915	0.625											-7.981	In-Between	0.203	Likely Benign	Likely Benign	7.63	Destabilizing	2.7	12.14	Destabilizing	9.89	Destabilizing	0.26	Likely Benign	0.635	Likely Pathogenic	-1.18	Neutral	1.000	Probably Damaging	0.996	Probably Damaging	1.32	Pathogenic	0.01	Affected			0.1595	0.4240		-3	-3	2.9	46.09
c.1209A>C	K403N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K403N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized) predict a pathogenic impact. Predictions from FoldX, Foldetta, and premPS are uncertain or inconclusive and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.275179	Structured	0.424920	Uncertain	0.960	0.372	0.000											-10.913	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.87	Ambiguous	0.1	0.41	Likely Benign	1.14	Ambiguous	0.74	Ambiguous	0.201	Likely Benign	-4.51	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.73	Benign	0.05	Affected			0.3374	0.2492		1	0	0.4	-14.07
c.1209A>T	K403N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K403N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized) predict a pathogenic impact. Predictions from FoldX, Foldetta, and premPS are uncertain or inconclusive and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.275179	Structured	0.424920	Uncertain	0.960	0.372	0.000											-10.913	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.87	Ambiguous	0.1	0.41	Likely Benign	1.14	Ambiguous	0.74	Ambiguous	0.201	Likely Benign	-4.51	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.73	Benign	0.05	Affected			0.3374	0.2492		1	0	0.4	-14.07
c.1244A>C	E415A 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E415A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, Rosetta, Foldetta, and FATHMM, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results are given by FoldX and premPS. High‑accuracy assessments indicate that AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Overall, the majority of tools lean toward pathogenicity, and the high‑accuracy predictions support this view. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.100716	Structured	0.330366	Uncertain	0.915	0.236	0.000											-11.743	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic	0.61	Ambiguous	0.2	0.05	Likely Benign	0.33	Likely Benign	0.53	Ambiguous	0.435	Likely Benign	-5.56	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.19	Benign	0.03	Affected			0.2909	0.3432		0	-1	5.3	-58.04
c.1256A>C	E419A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E419A missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM, whereas a majority of tools predict a pathogenic impact: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic classification; this conclusion does not contradict ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.371949	Uncertain	0.961	0.261	0.000											-10.951	Likely Pathogenic	0.944	Likely Pathogenic	Ambiguous	0.56	Ambiguous	0.1	0.94	Ambiguous	0.75	Ambiguous	0.28	Likely Benign	0.398	Likely Benign	-5.60	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.32	Benign	0.03	Affected			0.4051	0.6705		0	-1	5.3	-58.04
c.1265A>C	E422A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E422A missense variant is not reported in ClinVar and has no gnomAD entry. Prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM; pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized remains uncertain. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized is inconclusive; the SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates likely pathogenic; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts benign. Overall, the balance of evidence (seven pathogenic versus six benign predictions) points to a likely pathogenic effect for E422A, and this conclusion is not contradicted by the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.426709	Uncertain	0.965	0.255	0.000											-12.088	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	0.49	Likely Benign	0.0	0.25	Likely Benign	0.37	Likely Benign	0.26	Likely Benign	0.371	Likely Benign	-5.43	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.31	Benign	0.01	Affected			0.2949	0.4459		0	-1	5.3	-58.04
c.1309C>T	P437S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P437S is not reported in ClinVar (ClinVar ID: None) but is present in gnomAD (ID 6‑33438214‑C‑T). Prediction tools that agree on a benign effect include REVEL, Rosetta, FATHMM, and AlphaMissense‑Optimized, whereas PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b all predict a pathogenic outcome; the remaining methods (FoldX, Foldetta, premPS, AlphaMissense‑Default) are uncertain and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic interpretation. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.175930	Structured	0.306196	Uncertain	0.921	0.298	0.000								6-33438214-C-T	2	1.24e-6	-11.964	Likely Pathogenic	0.518	Ambiguous	Likely Benign	1.14	Ambiguous	0.0	-3.31	Stabilizing	-1.09	Ambiguous	0.60	Ambiguous	0.226	Likely Benign	-6.60	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.49	Benign	0.01	Affected	3.38	26	0.3548	0.4843		-1	1	0.8	-10.04
c.1310C>G	P437R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P437R is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, and FATHMM, whereas pathogenic predictions are made by SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. With the majority of tools indicating pathogenicity and the high‑accuracy consensus leaning toward pathogenic, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.306196	Uncertain	0.921	0.298	0.000											-13.094	Likely Pathogenic	0.879	Likely Pathogenic	Ambiguous	0.34	Likely Benign	0.1	-3.52	Stabilizing	-1.59	Ambiguous	0.61	Ambiguous	0.461	Likely Benign	-7.72	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.51	Benign	0.03	Affected			0.1448	0.2846		0	-2	-2.9	59.07
c.1310C>T	P437L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P437L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, and FATHMM. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. Predictions that are inconclusive or uncertain are FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts a likely pathogenic outcome, while AlphaMissense‑Optimized and Foldetta are uncertain. Taken together, the majority of evidence points toward a pathogenic impact for P437L, and this conclusion does not contradict the current ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.306196	Uncertain	0.921	0.298	0.000											-13.554	Likely Pathogenic	0.787	Likely Pathogenic	Ambiguous	1.10	Ambiguous	0.0	-3.52	Stabilizing	-1.21	Ambiguous	0.35	Likely Benign	0.324	Likely Benign	-8.48	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.67	Benign	0.04	Affected			0.2228	0.6354		-3	-3	5.4	16.04
c.1332G>C	K444N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K444N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the majority of tools (FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic impact. The high‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic; Foldetta’s stability assessment is uncertain and therefore not used as evidence. Overall, the preponderance of evidence points to a pathogenic effect for K444N. This conclusion is not contradicted by ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.203355	Structured	0.262172	Uncertain	0.955	0.213	0.000											-14.797	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.41	Destabilizing	0.0	1.52	Ambiguous	1.97	Ambiguous	1.18	Destabilizing	0.286	Likely Benign	-4.77	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.39	Benign	0.01	Affected			0.3282	0.1213		1	0	0.4	-14.07
c.1332G>T	K444N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K444N is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect are REVEL and FATHMM. Tools that predict a pathogenic effect include FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain predictions come from Rosetta and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic impact. There is no ClinVar annotation to contradict this assessment, so the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.203355	Structured	0.262172	Uncertain	0.955	0.213	0.000											-14.797	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.41	Destabilizing	0.0	1.52	Ambiguous	1.97	Ambiguous	1.18	Destabilizing	0.286	Likely Benign	-4.77	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.39	Benign	0.01	Affected			0.3282	0.1213		1	0	0.4	-14.07
c.1337A>C	E446A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E446A is not reported in ClinVar and is absent from gnomAD. In silico predictors that classify the variant as benign include REVEL, Rosetta, FATHMM, and AlphaMissense‑Optimized. Predictors that classify it as pathogenic comprise SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, yielded an inconclusive result and is treated as unavailable. Overall, the majority of predictions lean toward pathogenicity, and this conclusion is not contradicted by the absence of a ClinVar entry. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.276479	Uncertain	0.940	0.216	0.000											-9.868	Likely Pathogenic	0.677	Likely Pathogenic	Likely Benign	1.66	Ambiguous	0.7	0.39	Likely Benign	1.03	Ambiguous	0.67	Ambiguous	0.443	Likely Benign	-5.60	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	3.28	Benign	0.01	Affected			0.3195	0.5877		0	-1	5.3	-58.04
c.1373C>G	T458R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant T458R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, SIFT, and FATHMM, whereas a larger set—SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict pathogenicity. Uncertain results come from FoldX and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as benign. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.185198	Structured	0.294848	Uncertain	0.915	0.144	0.000											-12.984	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	-0.81	Ambiguous	0.1	-0.11	Likely Benign	-0.46	Likely Benign	0.61	Ambiguous	0.390	Likely Benign	-5.26	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.52	Benign	0.20	Tolerated			0.1016	0.3013		-1	-1	-3.8	55.08
c.1390T>G	F464V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F464V variant is listed in ClinVar with an “Uncertain” status (ClinVar ID 1716596.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM; all other evaluated algorithms (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the collective predictions, the variant is most likely pathogenic, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.313424	Uncertain	0.961	0.178	0.000					Uncertain		1				-12.254	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	3.61	Destabilizing	0.1	2.89	Destabilizing	3.25	Destabilizing	1.40	Destabilizing	0.592	Likely Pathogenic	-6.96	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	3.36	Benign	0.04	Affected	3.37	34	0.1587	0.2219		-1	-1	1.4	-48.04	210.1	40.5	-0.1	0.0	-0.9	0.3							X	Potentially Pathogenic	The phenyl ring of Phe464, located in the middle of an α helix (res. Ala461–Phe476), packs against hydrophobic residues (e.g., Met468, Leu451, Leu455, and Tyr428) in the inter-helix space formed with two other α helices (res. Asn440-Lys460 and res. Pro413-Glu436). The iso-propyl side chain of Val464 is similarly hydrophobic but considerably smaller than the original phenyl ring of Phe464. To compensate for the size difference, neighboring residues need to fill in the gap in the variant simulations.The phenolic side chain of Tyr428, located at the middle bend of an α helix (res. Glu436-Pro413), assumes a new position in the inter-helix space or rotates inward next to the third α helix (res. Asn440-Lys460) when the stable H-bond between Tyr428 and Asp467 seen in the WT simulations breaks. The residue swap also leads to the loss of the methionine-aromatic interaction between the Met468 and Phe464 side chains, which could weaken the integrity of the parent α helix (res. Ala461-Phe476). Although the simulations likely underestimate the full adverse effect of the introduced mutation during folding, the two opposing α helices (res. Ala461–Phe476 and res. Glu436-Pro413) move substantially closer to each other in the variant simulations.
c.1405G>C	A469P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A469P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only SIFT, whereas all other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenicity. Based on the overwhelming consensus of these predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.278302	Structured	0.343926	Uncertain	0.910	0.276	0.000											-16.072	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	5.06	Destabilizing	0.3	8.83	Destabilizing	6.95	Destabilizing	1.02	Destabilizing	0.774	Likely Pathogenic	-2.69	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	-1.33	Pathogenic	0.21	Tolerated			0.1606	0.4092		1	-1	-3.4	26.04
c.1406C>A	A469D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A469D is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that assess the variant’s effect fall into two groups: the single benign prediction from SIFT, and a consensus of pathogenic predictions from the remaining 15 tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus). High‑accuracy methods further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also indicates pathogenic. Taken together, the overwhelming majority of evidence points to a pathogenic effect, which is consistent with the ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.278302	Structured	0.343926	Uncertain	0.910	0.276	0.000					Uncertain		1				-14.643	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	5.09	Destabilizing	0.2	4.16	Destabilizing	4.63	Destabilizing	1.68	Destabilizing	0.738	Likely Pathogenic	-3.48	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	-1.34	Pathogenic	0.21	Tolerated	3.37	34	0.1372	0.1583		0	-2	-5.3	44.01	237.0	-58.2	-0.2	0.1	0.8	0.1	X		X					Potentially Pathogenic	The methyl group of Ala469, located in an α helix (res. Ala461–Phe476), interacts with hydrophobic residues (e.g., Trp572, Leu588, Met470) in an inter-helix space formed by two other α helices (res. Glu582–Ser604, res. Arg563–Gly580). In the variant simulations, Asp469 introduces a negatively charged and bulky side chain into the hydrophobic niche. Consequently, the side chain of Asp469 rotates outward, allowing the carboxylate group to form a salt bridge with the guanidinium group of Arg575 on the protein surface. This interaction affects the continuity of the parent α helix (Ala461–Phe476). Due to the importance of hydrophobic packing, the structural effects could be more pronounced during actual protein folding.
c.1443C>A	H481Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 H481Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, and FATHMM; pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy methods give a mixed signal: AlphaMissense‑Optimized classifies the variant as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Overall, the balance of evidence leans toward a benign effect, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.257454	Structured	0.430977	Uncertain	0.764	0.247	0.000											-8.524	Likely Pathogenic	0.663	Likely Pathogenic	Likely Benign	-0.41	Likely Benign	0.1	0.31	Likely Benign	-0.05	Likely Benign	0.32	Likely Benign	0.243	Likely Benign	-4.11	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.55	Benign	0.51	Tolerated			0.1052	0.2797		3	0	-0.3	-9.01
c.1443C>G	H481Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 H481Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, and FATHMM; pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy methods give a mixed signal: AlphaMissense‑Optimized classifies the variant as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Overall, the balance of evidence leans toward a benign effect, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.257454	Structured	0.430977	Uncertain	0.764	0.247	0.000											-8.524	Likely Pathogenic	0.663	Likely Pathogenic	Likely Benign	-0.41	Likely Benign	0.1	0.31	Likely Benign	-0.05	Likely Benign	0.32	Likely Benign	0.243	Likely Benign	-4.11	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.55	Benign	0.51	Tolerated			0.1052	0.2797		3	0	-0.3	-9.01
c.1445T>G	L482R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L482R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate pathogenicity, while FoldX, Rosetta, and Foldetta return uncertain results. In a consensus framework, the SGM‑Consensus score is “Likely Pathogenic,” reflecting the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN. High‑accuracy assessments further support a damaging outcome: AlphaMissense‑Optimized predicts pathogenicity, SGM‑Consensus is Likely Pathogenic, and Foldetta remains inconclusive. Taken together, the overwhelming majority of evidence points to a pathogenic effect. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.426236	Uncertain	0.795	0.248	0.000											-14.684	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.74	Ambiguous	0.1	1.31	Ambiguous	1.03	Ambiguous	1.53	Destabilizing	0.878	Likely Pathogenic	-5.92	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	-1.27	Pathogenic	0.01	Affected			0.1255	0.0679		-3	-2	-8.3	43.03
c.1459A>C	N487H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N487H has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, while the majority of tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus) predict a pathogenic or likely pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No evidence from these tools contradicts the lack of ClinVar annotation. Overall, the preponderance of pathogenic predictions indicates that the variant is most likely pathogenic, consistent with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.209395	Structured	0.338511	Uncertain	0.890	0.243	0.125											-11.403	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	1.15	Ambiguous	0.1	0.84	Ambiguous	1.00	Ambiguous	0.72	Ambiguous	0.548	Likely Pathogenic	-4.97	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.68	Benign	0.00	Affected			0.1123	0.3411		2	1	0.3	23.04
c.1463C>A	T488K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T488K is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, while the remaining eleven tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) all classify the variant as pathogenic. The high‑accuracy methods—AlphaMissense‑Optimized, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta (combining FoldX‑MD and Rosetta outputs)—all predict pathogenicity. No prediction or folding‑stability result is missing or inconclusive. Based on the consensus of these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.332663	Uncertain	0.928	0.233	0.125											-14.391	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	2.09	Destabilizing	0.2	2.33	Destabilizing	2.21	Destabilizing	0.90	Ambiguous	0.692	Likely Pathogenic	-5.64	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.24	Benign	0.00	Affected			0.0871	0.2104		0	-1	-3.2	27.07
c.1484A>T	E495V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E495V is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, and premPS, whereas the majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further show AlphaMissense‑Optimized as pathogenic, the SGM Consensus as likely pathogenic, and Foldetta as benign. Taken together, the preponderance of evidence (10 pathogenic‑predicted tools versus 4 benign) indicates that E495V is most likely pathogenic. This conclusion does not contradict ClinVar status, as the variant is currently unreported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.164327	Structured	0.364496	Uncertain	0.933	0.161	0.000											-12.031	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.43	Likely Benign	0.2	-0.32	Likely Benign	0.06	Likely Benign	0.47	Likely Benign	0.887	Likely Pathogenic	-6.83	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	-1.44	Pathogenic	0.00	Affected			0.0646	0.5457		-2	-2	7.7	-29.98
c.1487A>T	E496V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E496V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from FoldX, Foldetta, and premPS, while pathogenic calls are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments give mixed results: AlphaMissense‑Optimized is Uncertain; SGM‑Consensus remains Likely Pathogenic; Foldetta, a folding‑stability predictor that integrates FoldX‑MD and Rosetta outputs, classifies the variant as Benign. Because the variant is not present in ClinVar, there is no clinical annotation to contradict the computational evidence. Overall, the preponderance of pathogenic predictions, including the consensus score, suggests that E496V is most likely pathogenic, though the conflicting high‑accuracy folding stability result indicates uncertainty that warrants further functional validation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.383296	Uncertain	0.945	0.179	0.000											-14.290	Likely Pathogenic	0.873	Likely Pathogenic	Ambiguous	0.17	Likely Benign	0.1	-0.67	Ambiguous	-0.25	Likely Benign	0.26	Likely Benign	0.823	Likely Pathogenic	-6.16	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	-1.43	Pathogenic	0.02	Affected			0.0556	0.3746		-2	-2	7.7	-29.98
c.1514A>T	Y505F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y505F is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Predictions that are uncertain or inconclusive are Rosetta, Foldetta, premPS, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of tools (five benign versus four pathogenic) lean toward a benign interpretation, and this is consistent with the lack of ClinVar evidence; thus the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.047319	Structured	0.292227	Uncertain	0.909	0.188	0.000											-8.855	Likely Pathogenic	0.437	Ambiguous	Likely Benign	0.40	Likely Benign	0.0	0.76	Ambiguous	0.58	Ambiguous	0.69	Ambiguous	0.434	Likely Benign	-3.98	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.93	Benign	0.07	Tolerated			0.2409	0.2598		7	3	4.1	-16.00
c.1530T>G	I510M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I510M missense variant is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign impact include PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict pathogenicity are REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The remaining tools (FoldX, Rosetta, Foldetta, premPS, ESM1b) returned uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (benign), ESM1b (uncertain), FATHMM (pathogenic), and PROVEAN (benign)—also favors benign. Foldetta, a protein‑folding stability method, yielded an uncertain outcome. Taken together, the consensus of the most reliable predictors indicates a benign effect. This conclusion does not contradict the ClinVar status, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.025762	Structured	0.250630	Uncertain	0.945	0.273	0.000											-7.988	In-Between	0.235	Likely Benign	Likely Benign	0.56	Ambiguous	0.3	1.61	Ambiguous	1.09	Ambiguous	0.55	Ambiguous	0.532	Likely Pathogenic	-0.97	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	-1.42	Pathogenic	0.02	Affected			0.0674	0.1789		2	1	-2.6	18.03
c.1553A>T	Y518F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 Y518F missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, AlphaMissense‑Optimized, and Foldetta. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Two tools are uncertain: Rosetta and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Overall, the majority of individual predictors (seven benign vs. four pathogenic) support a benign classification, and this does not contradict the ClinVar status, which has no entry for this variant. Thus, based on the available predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.139895	Structured	0.126970	Uncertain	0.897	0.321	0.000											-10.617	Likely Pathogenic	0.466	Ambiguous	Likely Benign	0.34	Likely Benign	0.1	-0.61	Ambiguous	-0.14	Likely Benign	0.41	Likely Benign	0.318	Likely Benign	-3.68	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.50	Benign	0.22	Tolerated			0.2107	0.2230		7	3	4.1	-16.00
c.1559C>A	S520Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S520Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include Rosetta and Foldetta, whereas the majority of algorithms predict pathogenicity: SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools give inconclusive results: FoldX (Uncertain) and premPS (Uncertain). High‑accuracy assessments further support a mixed signal: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus indicates likely pathogenic, and Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts benign. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.094817	Structured	0.084894	Uncertain	0.887	0.337	0.000											-13.124	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	-0.93	Ambiguous	0.4	0.16	Likely Benign	-0.39	Likely Benign	0.59	Ambiguous	0.814	Likely Pathogenic	-5.57	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	-1.36	Pathogenic	0.00	Affected			0.0743	0.4563		-3	-2	-0.5	76.10
c.1559C>T	S520F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S520F is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools that classify the variant as benign include Rosetta, Foldetta, and premPS. Those that predict pathogenicity are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX gives an uncertain result. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, whereas Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a benign impact. Overall, the majority of evidence points to a pathogenic effect, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.094817	Structured	0.084894	Uncertain	0.887	0.337	0.000					Uncertain		1				-12.541	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	-1.20	Ambiguous	0.4	0.39	Likely Benign	-0.41	Likely Benign	0.25	Likely Benign	0.833	Likely Pathogenic	-5.57	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	-1.36	Pathogenic	0.00	Affected	3.37	35	0.0668	0.4779		-2	-3	3.6	60.10
c.1562A>T	E521V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E521V missense change is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy AlphaMissense‑Optimized score is pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a benign outcome. Overall, the majority of evidence points to a pathogenic impact for E521V, and this assessment does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-10.297	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.31	Likely Benign	0.1	0.49	Likely Benign	0.40	Likely Benign	0.21	Likely Benign	0.413	Likely Benign	-5.15	Deleterious	0.995	Probably Damaging	0.996	Probably Damaging	3.26	Benign	0.05	Affected			0.0913	0.7104		-2	-2	7.7	-29.98
c.1565A>T	E522V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E522V missense change is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, and premPS, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic; and Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.046216	Uncertain	0.823	0.376	0.000											-11.985	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.09	Likely Benign	0.2	0.00	Likely Benign	0.05	Likely Benign	0.18	Likely Benign	0.751	Likely Pathogenic	-6.59	Deleterious	0.995	Probably Damaging	0.996	Probably Damaging	-1.31	Pathogenic	0.01	Affected			0.0537	0.4514		-2	-2	7.7	-29.98
c.1582C>A	P528T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P528T is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tools predict a benign outcome. Predictions that are uncertain or inconclusive are Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as Uncertain. Based on the preponderance of pathogenic predictions and the lack of benign evidence, the variant is most likely pathogenic. This conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.225814	Structured	0.020396	Uncertain	0.909	0.403	0.000											-13.782	Likely Pathogenic	0.798	Likely Pathogenic	Ambiguous	2.05	Destabilizing	0.3	1.01	Ambiguous	1.53	Ambiguous	0.66	Ambiguous	0.673	Likely Pathogenic	-7.69	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.49	Pathogenic	0.00	Affected			0.1367	0.4360		0	-1	0.9	3.99
c.1643A>T	E548V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E548V missense variant is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that indicate a benign effect include FoldX, Rosetta, Foldetta, premPS, and FATHMM. In contrast, tools predicting a pathogenic impact are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of predictions (10 pathogenic vs. 5 benign) support a pathogenic classification. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.054297	Structured	0.008632	Uncertain	0.965	0.288	0.000											-15.029	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.29	Likely Benign	0.0	-0.18	Likely Benign	0.06	Likely Benign	0.36	Likely Benign	0.578	Likely Pathogenic	-6.83	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.24	Benign	0.02	Affected			0.0569	0.4714		-2	-2	7.7	-29.98
c.1670C>A	S557Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S557Y is not reported in ClinVar and has no gnomAD entry. Prediction tools largely agree on a deleterious effect: all except premPS (which predicts benign) return pathogenic or likely pathogenic. The high‑accuracy methods reinforce this: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels it likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. No tool indicates a benign outcome. Consequently, the variant is most likely pathogenic according to the available computational evidence, and this assessment does not conflict with ClinVar status, which currently contains no entry for S557Y. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.028107	Structured	0.010261	Uncertain	0.924	0.215	0.000											-13.792	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	18.89	Destabilizing	1.1	3.48	Destabilizing	11.19	Destabilizing	-0.20	Likely Benign	0.965	Likely Pathogenic	-5.45	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	-1.77	Pathogenic	0.00	Affected			0.1157	0.6087		-3	-2	-0.5	76.10
c.1670C>T	S557F 2D AIThe SynGAP1 missense variant S557F is not reported in ClinVar and has no gnomAD entry. Prediction tools cluster into two groups: the single benign prediction from premPS versus a consensus of pathogenic predictions from the remaining 13 tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized). High‑accuracy methods—AlphaMissense‑Optimized, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta—all indicate pathogenicity. No prediction or stability result is missing or inconclusive. Consequently, the variant is most likely pathogenic based on the aggregate computational evidence, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.028107	Structured	0.010261	Uncertain	0.924	0.215	0.000											-12.523	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	15.55	Destabilizing	5.2	9.95	Destabilizing	12.75	Destabilizing	0.08	Likely Benign	0.958	Likely Pathogenic	-5.38	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	-1.77	Pathogenic	0.00	Affected			0.1073	0.5931		-3	-2	3.6	60.10
c.1675T>C	C559R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C559R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, Rosetta, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Uncertain or inconclusive results come from FoldX, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of tools (six pathogenic vs five benign) lean toward a pathogenic interpretation, and this does not contradict any ClinVar status because the variant is not yet classified in ClinVar. Thus, the variant is most likely pathogenic based on current predictive evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.016021	Structured	0.010460	Uncertain	0.842	0.204	0.000											-9.509	Likely Pathogenic	0.779	Likely Pathogenic	Likely Benign	-1.03	Ambiguous	0.1	-0.38	Likely Benign	-0.71	Ambiguous	0.79	Ambiguous	0.498	Likely Benign	-8.58	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.48	Benign	0.46	Tolerated			0.2498	0.1720		-4	-3	-7.0	53.05
c.1676G>A	C559Y 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant C559Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, premPS, SIFT, and FATHMM. Those that predict pathogenicity are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Because the evidence is split evenly between benign and pathogenic predictions and the high‑accuracy tools disagree, the variant is best classified as of uncertain significance. This assessment does not contradict ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.016021	Structured	0.010460	Uncertain	0.842	0.204	0.000											-11.767	Likely Pathogenic	0.868	Likely Pathogenic	Ambiguous	-0.37	Likely Benign	0.0	-0.19	Likely Benign	-0.28	Likely Benign	0.36	Likely Benign	0.561	Likely Pathogenic	-8.39	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.45	Benign	0.10	Tolerated			0.2094	0.2135		0	-2	-3.8	60.04
c.1676G>T	C559F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C559F is not reported in ClinVar (ClinVar ID = None) and has no entry in gnomAD (gnomAD ID = None). Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the predictions are split evenly, but the two most reliable tools (AlphaMissense‑Optimized and Foldetta) both indicate a benign effect, whereas the consensus pathogenic tool is a single outlier. Thus, the variant is most likely benign based on the current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.016021	Structured	0.010460	Uncertain	0.842	0.204	0.000											-13.194	Likely Pathogenic	0.779	Likely Pathogenic	Likely Benign	-0.43	Likely Benign	0.0	-0.04	Likely Benign	-0.24	Likely Benign	0.29	Likely Benign	0.576	Likely Pathogenic	-8.48	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.43	Benign	0.09	Tolerated			0.2234	0.2653		-4	-2	0.3	44.04
c.1700A>T	E567V 2D 3DClick to see structure in 3D Viewer AISynGAP1 E567V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, FoldX, premPS, SIFT, FATHMM) and pathogenic predictions (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default). High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, while Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts benign. Rosetta alone is inconclusive and treated as unavailable. Overall, the majority of evidence points to a pathogenic effect for E567V, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.021816	Structured	0.051008	Uncertain	0.916	0.234	0.000											-15.638	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	0.27	Likely Benign	0.1	0.59	Ambiguous	0.43	Likely Benign	0.38	Likely Benign	0.440	Likely Benign	-6.77	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.48	Benign	0.06	Tolerated			0.0573	0.6175		-2	-2	7.7	-29.98
c.1712C>T	S571L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S571L is listed in ClinVar with an uncertain significance (ClinVar ID 3897075) and is present in gnomAD (ID 6‑33440764‑C‑T). Prediction tools that indicate a benign effect include premPS and AlphaMissense‑Optimized, whereas the remaining tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) all predict a pathogenic outcome. The high‑accuracy AlphaMissense‑Optimized score is benign, whereas the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—supports pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, is inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for S571L, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.069024	Structured	0.045569	Uncertain	0.928	0.270	0.000					Uncertain		2	6-33440764-C-T	1	6.23e-7	-11.651	Likely Pathogenic	0.660	Likely Pathogenic	Likely Benign	-1.53	Ambiguous	0.1	-1.05	Ambiguous	-1.29	Ambiguous	0.27	Likely Benign	0.841	Likely Pathogenic	-5.61	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	-1.25	Pathogenic	0.04	Affected	3.37	35	0.0959	0.3918		-2	-3	4.6	26.08
c.1726T>C	C576R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant C576R is listed in ClinVar with an uncertain significance (ClinVar ID 2780076.0) and is not reported in gnomAD. Prediction tools that classify the variant as benign include only FATHMM. All other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—predict it to be pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores it pathogenic, the SGM‑Consensus (derived from the majority of high‑confidence predictors) is pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. Taken together, the overwhelming majority of computational evidence indicates that C576R is likely pathogenic, a conclusion that is consistent with, but not in conflict with, the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.017684	Uncertain	0.913	0.245	0.000					Conflicting		2				-14.886	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	7.20	Destabilizing	1.0	4.09	Destabilizing	5.65	Destabilizing	1.64	Destabilizing	0.579	Likely Pathogenic	-10.88	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.38	Benign	0.00	Affected	3.37	35	0.1887	0.1279		-3	-4	-7.0	53.05
c.1727G>A	C576Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C576Y is not reported in ClinVar and has no gnomAD allele. Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, whereas SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default and AlphaMissense‑Optimized all classify the change as pathogenic. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports a likely pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also indicates pathogenicity. No tool yields an inconclusive result. Based on the consensus of available predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.017684	Uncertain	0.913	0.245	0.000											-13.891	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	8.77	Destabilizing	0.5	3.90	Destabilizing	6.34	Destabilizing	0.63	Ambiguous	0.612	Likely Pathogenic	-9.98	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.38	Benign	0.00	Affected			0.1398	0.3009		0	-2	-3.8	60.04
c.1727G>T	C576F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C576F is not reported in ClinVar (ClinVar ID = None) and has no entries in gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect are limited to FATHMM, which scores the variant as benign. All other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and Foldetta—consistently predict a pathogenic or likely pathogenic impact. Uncertain predictions from Rosetta and premPS are treated as unavailable. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized reports pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Based on the overwhelming agreement among high‑confidence tools, the variant is most likely pathogenic, and this assessment does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.017684	Uncertain	0.913	0.245	0.000											-13.467	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	5.04	Destabilizing	0.5	1.81	Ambiguous	3.43	Destabilizing	0.58	Ambiguous	0.516	Likely Pathogenic	-9.93	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.40	Benign	0.02	Affected			0.1626	0.3527		-4	-2	0.3	44.04
c.1730C>A	A577E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A577E missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, and SIFT, whereas those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while Foldetta (combining FoldX‑MD and Rosetta outputs) is also uncertain; Rosetta and premPS are inconclusive. Overall, the majority of evaluated tools (five pathogenic vs. four benign) and the SGM‑Consensus support a pathogenic classification. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.019074	Uncertain	0.913	0.239	0.000											-9.607	Likely Pathogenic	0.794	Likely Pathogenic	Ambiguous	0.29	Likely Benign	0.0	0.72	Ambiguous	0.51	Ambiguous	0.62	Ambiguous	0.419	Likely Benign	-1.91	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	-1.12	Pathogenic	0.76	Tolerated			0.1487	0.1799		0	-1	-5.3	58.04
c.1745A>T	E582V 2D 3DClick to see structure in 3D Viewer AISynGAP1 E582V is not reported in ClinVar and is absent from gnomAD. Computational predictors show a split: benign calls from REVEL, Rosetta, premPS, SIFT, and FATHMM; pathogenic calls from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default; and two uncertain calls from FoldX and AlphaMissense‑Optimized. High‑accuracy methods give a pathogenic consensus: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is uncertain due to conflicting inputs. Overall, the computational evidence leans toward pathogenicity, and this assessment does not contradict ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.033838	Uncertain	0.845	0.235	0.000											-10.737	Likely Pathogenic	0.842	Likely Pathogenic	Ambiguous	0.87	Ambiguous	0.1	-0.13	Likely Benign	0.37	Likely Benign	0.24	Likely Benign	0.251	Likely Benign	-3.92	Deleterious	0.995	Probably Damaging	0.996	Probably Damaging	3.15	Benign	0.10	Tolerated			0.0564	0.4186		-2	-2	7.7	-29.98
c.1753G>T	A585S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A585S is not reported in ClinVar (no entry) and is absent from gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. FoldX, Rosetta, and Foldetta are inconclusive. High‑accuracy methods give a benign consensus: AlphaMissense‑Optimized predicts benign, SGM‑Consensus predicts Likely Benign, while Foldetta remains uncertain. Overall, the majority of evidence supports a benign classification, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.060549	Structured	0.055884	Uncertain	0.880	0.244	0.000											-6.332	Likely Benign	0.246	Likely Benign	Likely Benign	0.91	Ambiguous	0.2	1.44	Ambiguous	1.18	Ambiguous	0.02	Likely Benign	0.326	Likely Benign	0.39	Neutral	0.993	Probably Damaging	0.996	Probably Damaging	-1.27	Pathogenic	0.98	Tolerated			0.2121	0.3388		1	1	-2.6	16.00
c.1805T>C	I602T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I602T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify it as pathogenic or likely pathogenic. No tool reports a benign outcome. High‑accuracy assessments corroborate this trend: AlphaMissense‑Optimized is uncertain, SGM‑Consensus is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenicity. Consequently, the variant is most likely pathogenic according to the available computational evidence, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.010221	Structured	0.186541	Uncertain	0.963	0.171	0.000											-12.238	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous	2.39	Destabilizing	0.1	2.14	Destabilizing	2.27	Destabilizing	1.94	Destabilizing	0.931	Likely Pathogenic	-4.82	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	-2.00	Pathogenic	0.00	Affected			0.0890	0.0989		0	-1	-5.2	-12.05
c.1841A>T	Y614F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y614F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Uncertain or unavailable results come from Foldetta, premPS, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta is unavailable. Overall, the majority of reliable predictors indicate a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.314870	Structured	0.182134	Uncertain	0.852	0.254	0.000											-5.584	Likely Benign	0.630	Likely Pathogenic	Likely Benign	0.09	Likely Benign	0.2	0.98	Ambiguous	0.54	Ambiguous	0.78	Ambiguous	0.364	Likely Benign	-3.75	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.42	Benign	0.07	Tolerated			0.1909	0.2762		7	3	4.1	-16.00
c.1871C>A	T624N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T624N is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include FoldX and Foldetta, whereas the majority of tools predict a pathogenic impact: REVEL, SIFT, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM Consensus (which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Uncertain results come from AlphaMissense‑Optimized, Rosetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus as likely pathogenic, and Foldetta as benign. Overall, the balance of evidence favors a pathogenic classification for T624N, and this conclusion does not contradict any ClinVar annotation because no ClinVar status is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.137348	Structured	0.052894	Uncertain	0.962	0.217	0.000											-14.658	Likely Pathogenic	0.915	Likely Pathogenic	Ambiguous	-0.24	Likely Benign	0.0	0.87	Ambiguous	0.32	Likely Benign	0.97	Ambiguous	0.848	Likely Pathogenic	-4.94	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	-1.53	Pathogenic	0.00	Affected			0.0773	0.2694		0	0	-2.8	13.00
c.1900G>C	A634P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A634P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools largely agree on a deleterious effect: benign predictions are limited to FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the consensus of these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.085092	Structured	0.052058	Uncertain	0.932	0.242	0.000											-15.372	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	4.17	Destabilizing	0.2	7.72	Destabilizing	5.95	Destabilizing	1.39	Destabilizing	0.745	Likely Pathogenic	-4.98	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.50	Benign	0.01	Affected			0.2090	0.3429		1	-1	-3.4	26.04
c.1901C>A	A634D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A634D is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that assess pathogenicity all agree on a deleterious effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. No tool predicts a benign outcome. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates pathogenicity; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, reports a pathogenic effect. No predictions or stability results are missing or inconclusive. Based on the unanimous computational evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.085092	Structured	0.052058	Uncertain	0.932	0.242	0.000											-16.727	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	5.26	Destabilizing	0.5	4.24	Destabilizing	4.75	Destabilizing	1.79	Destabilizing	0.731	Likely Pathogenic	-5.98	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.49	Pathogenic	0.00	Affected			0.1790	0.1816		0	-2	-5.3	44.01
c.1958T>C	L653P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L653P is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.049374	Structured	0.335213	Uncertain	0.963	0.332	0.000											-17.675	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	6.02	Destabilizing	0.8	9.20	Destabilizing	7.61	Destabilizing	2.56	Destabilizing	0.700	Likely Pathogenic	-6.51	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.09	Benign	0.00	Affected			0.3251	0.1874		-3	-3	-5.4	-16.04
c.1990T>A	L664M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L664M is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, and FATHMM, while those that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is also uncertain due to a 2‑vs‑2 split; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain. Overall, the majority of conventional tools predict a pathogenic impact, whereas the high‑accuracy methods do not provide a definitive verdict. Consequently, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.100716	Structured	0.089318	Uncertain	0.937	0.339	0.000											-11.819	Likely Pathogenic	0.807	Likely Pathogenic	Ambiguous	0.49	Likely Benign	0.1	1.35	Ambiguous	0.92	Ambiguous	0.96	Ambiguous	0.429	Likely Benign	-2.00	Neutral	1.000	Probably Damaging	0.996	Probably Damaging	2.92	Benign	0.01	Affected			0.0620	0.2541		4	2	-1.9	18.03
c.1991T>C	L664S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L664S is listed in ClinVar as Benign (ClinVar ID 2429773.0) and is present in gnomAD (ID 6‑33441250‑T‑C). Prediction tools that report a benign effect include only FATHMM; all other evaluated algorithms (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact, and the SGM‑Consensus score is “Likely Pathogenic.” High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Pathogenic. Based on the overwhelming majority of pathogenic predictions—including the high‑accuracy tools—the variant is most likely pathogenic, which contradicts its ClinVar benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.100716	Structured	0.089318	Uncertain	0.937	0.339	0.000					Likely Benign		1	6-33441250-T-C	1	6.20e-7	-16.498	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	3.75	Destabilizing	0.2	3.63	Destabilizing	3.69	Destabilizing	2.77	Destabilizing	0.543	Likely Pathogenic	-5.99	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.85	Benign	0.00	Affected	3.38	28	0.2091	0.0896		-3	-2	-4.6	-26.08	215.5	50.1	0.0	0.0	-0.2	0.2						X		Potentially Benign	The iso-butyl side chain of L664, located on an α-helix (res. Ser641-Glu666), hydrophobically interacts with residues in the inter-helix space between three helices (res. Glu617-Asn635, res. Glu582-Met603, and res. Ser641-Glu666), such as Ile589, Phe663, and Met660. In the variant simulations, the hydroxyl group of Ser664 forms hydrogen bonds with the backbone carbonyl oxygen of another helix residue, such as Met660 or Gln661. This interaction is known to destabilize hydrogen bonding in the α-helix, but this effect was not observed in the simulations. Additionally, Ser664 occasionally forms hydrogen bonds with the carboxylate group of Asp586 on another α-helix (res. Glu582-Met603), which could minimally influence the tertiary structure assembly. Despite these interactions, no major negative effects on the protein structure were observed during the simulations.
c.1993T>A	Y665N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 Y665N variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Default) give uncertain results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of conventional predictors lean toward a benign impact, and this assessment does not contradict ClinVar status (none). Thus, the variant is most likely benign based on the prevailing predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.098513	Structured	0.086641	Uncertain	0.922	0.361	0.000											-11.189	Likely Pathogenic	0.470	Ambiguous	Likely Benign	1.11	Ambiguous	0.1	1.43	Ambiguous	1.27	Ambiguous	0.50	Likely Benign	0.219	Likely Benign	-3.03	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.50	Benign	0.88	Tolerated			0.1929	0.0573		-2	-2	-2.2	-49.07
c.1993T>C	Y665H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y665H is not reported in ClinVar (ClinVar status: not reported) but is present in gnomAD (gnomAD ID: 6‑33441252‑T‑C). Prediction tools that agree on a benign effect include REVEL, Rosetta, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Tools with uncertain or inconclusive results are FoldX, Foldetta, and AlphaMissense‑Default. High‑accuracy methods give a benign consensus: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, and Foldetta remains uncertain. Overall, the majority of predictions (7 benign vs. 4 pathogenic) and the high‑accuracy consensus support a benign classification. This conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.098513	Structured	0.086641	Uncertain	0.922	0.361	0.000								6-33441252-T-C	2	1.24e-6	-9.303	Likely Pathogenic	0.389	Ambiguous	Likely Benign	0.85	Ambiguous	0.0	0.28	Likely Benign	0.57	Ambiguous	1.12	Destabilizing	0.129	Likely Benign	-2.00	Neutral	1.000	Probably Damaging	0.996	Probably Damaging	3.45	Benign	0.48	Tolerated	3.38	28	0.2122	0.0513		2	0	-1.9	-26.03
c.1993T>G	Y665D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y665D is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as Uncertain. No evidence from these tools contradicts the ClinVar status, which is currently unreported. Overall, the balance of evidence—seven pathogenic versus four benign predictions, with a pathogenic consensus from SGM‑Consensus—suggests the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.098513	Structured	0.086641	Uncertain	0.922	0.361	0.000											-10.101	Likely Pathogenic	0.737	Likely Pathogenic	Likely Benign	1.15	Ambiguous	0.2	1.30	Ambiguous	1.23	Ambiguous	0.15	Likely Benign	0.227	Likely Benign	-3.67	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.75	Benign	1.00	Tolerated			0.3838	0.0573		-4	-3	-2.2	-48.09
c.2006A>T	N669I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N669I is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include premPS and FATHMM, whereas the remaining ten tools—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the majority‑vote SGM‑Consensus—predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain (treated as unavailable), SGM‑Consensus as likely pathogenic, and Foldetta as uncertain (also treated as unavailable). The overall consensus of the available predictions leans strongly toward pathogenicity, and this conclusion does not conflict with the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.142424	Structured	0.086615	Uncertain	0.872	0.380	0.000											-13.324	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous	0.84	Ambiguous	0.0	1.09	Ambiguous	0.97	Ambiguous	0.31	Likely Benign	0.517	Likely Pathogenic	-8.18	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.34	Benign	0.00	Affected			0.0749	0.4697		-2	-3	8.0	-0.94
c.2009T>C	L670P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L670P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. Stability‑based methods are inconclusive: FoldX, Rosetta, and the combined Foldetta output are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the majority of evidence supports a benign classification, and this is consistent with the absence of a ClinVar assertion; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.161087	Structured	0.090855	Uncertain	0.812	0.385	0.000											-4.916	Likely Benign	0.237	Likely Benign	Likely Benign	0.56	Ambiguous	0.3	1.83	Ambiguous	1.20	Ambiguous	-0.25	Likely Benign	0.211	Likely Benign	2.42	Neutral	1.000	Probably Damaging	0.996	Probably Damaging	3.41	Benign	0.26	Tolerated			0.3590	0.1474		-3	-3	-5.4	-16.04
c.2045A>G	Y682C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y682C is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default all predict pathogenicity, while only FATHMM predicts a benign outcome. The remaining tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) are uncertain. High‑accuracy assessments reinforce this trend: the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic; AlphaMissense‑Optimized is uncertain; and Foldetta is uncertain. Overall, the preponderance of evidence points to a pathogenic impact for Y682C. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.141467	Uncertain	0.758	0.328	0.000											-10.023	Likely Pathogenic	0.793	Likely Pathogenic	Ambiguous	1.79	Ambiguous	0.1	1.51	Ambiguous	1.65	Ambiguous	1.11	Destabilizing	0.559	Likely Pathogenic	-8.71	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.33	Benign	0.01	Affected			0.2949	0.2399		0	-2	3.8	-60.04
c.2053T>A	L685M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L685M is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, and FATHMM, whereas those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. Uncertain predictions come from premPS, Foldetta, Rosetta, and AlphaMissense‑Optimized. High‑accuracy methods give inconclusive results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑to‑2 tie and therefore uncertain; Foldetta also reports an uncertain stability change. Consequently, the overall computational evidence is mixed, with a slight tilt toward pathogenicity. Thus, the variant is most likely pathogenic based on predictions, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.175930	Structured	0.162061	Uncertain	0.913	0.280	0.000											-10.790	Likely Pathogenic	0.902	Likely Pathogenic	Ambiguous	0.35	Likely Benign	0.1	1.01	Ambiguous	0.68	Ambiguous	0.83	Ambiguous	0.281	Likely Benign	-2.00	Neutral	1.000	Probably Damaging	0.996	Probably Damaging	3.29	Benign	0.01	Affected			0.0814	0.2758		4	2	-1.9	18.03
c.2054T>C	L685S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L685S is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenic. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.162061	Uncertain	0.913	0.280	0.000											-12.303	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.08	Destabilizing	0.2	2.95	Destabilizing	3.02	Destabilizing	1.24	Destabilizing	0.520	Likely Pathogenic	-5.99	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.27	Benign	0.01	Affected			0.2844	0.0505		-3	-2	-4.6	-26.08
c.2063A>C	E688A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E688A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Foldetta, and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; FoldX, Rosetta, and premPS are inconclusive. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates likely pathogenic; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts benign. Overall, the majority of evidence points to a pathogenic effect for E688A. This conclusion is consistent with the absence of ClinVar annotation, so there is no contradiction with existing clinical databases. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.211124	Uncertain	0.947	0.223	0.000											-13.556	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	0.55	Ambiguous	0.5	-0.53	Ambiguous	0.01	Likely Benign	0.68	Ambiguous	0.495	Likely Benign	-5.55	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.26	Benign	0.01	Affected			0.3806	0.5296		0	-1	5.3	-58.04
c.2074C>A	L692M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L692M is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2) and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. Thus, the overall evidence slightly favors pathogenicity, with a majority of standard tools predicting a deleterious impact. The variant is most likely pathogenic based on current predictions, and this assessment does not contradict the ClinVar status, which has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.064632	Structured	0.295225	Uncertain	0.966	0.243	0.000											-9.659	Likely Pathogenic	0.746	Likely Pathogenic	Likely Benign	0.49	Likely Benign	0.0	1.81	Ambiguous	1.15	Ambiguous	1.01	Destabilizing	0.302	Likely Benign	-1.99	Neutral	1.000	Probably Damaging	0.996	Probably Damaging	3.07	Benign	0.01	Affected			0.0754	0.2585		4	2	-1.9	18.03
c.2078A>C	H693P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H693P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are limited to FATHMM, which classifies the variant as benign. All other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic or likely pathogenic impact. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.073402	Structured	0.323991	Uncertain	0.964	0.260	0.000											-16.281	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	5.54	Destabilizing	0.2	6.09	Destabilizing	5.82	Destabilizing	1.06	Destabilizing	0.600	Likely Pathogenic	-9.97	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.09	Benign	0.01	Affected			0.2080	0.3210		0	-2	1.6	-40.02
c.2108T>C	L703P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L703P is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic, while only FATHMM predicts it benign. The SGM‑Consensus, which is a majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Pathogenic” result (3 pathogenic vs. 1 benign). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; SGM‑Consensus is likely pathogenic; and Foldetta, integrating FoldX‑MD and Rosetta outputs, is pathogenic. No prediction or stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.144935	Structured	0.388282	Uncertain	0.929	0.353	0.000											-13.766	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	4.44	Destabilizing	0.1	9.38	Destabilizing	6.91	Destabilizing	1.54	Destabilizing	0.559	Likely Pathogenic	-5.70	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.11	Benign	0.00	Affected			0.3698	0.1186		-3	-3	-5.4	-16.04
c.2179A>C	N727H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N727H is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Two tools (premPS and ESM1b) return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of predictions (six benign vs. five pathogenic) lean toward a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.538167	Disordered	0.442107	Uncertain	0.843	0.542	0.625											-7.308	In-Between	0.224	Likely Benign	Likely Benign	0.13	Likely Benign	0.0	-0.02	Likely Benign	0.06	Likely Benign	0.51	Ambiguous	0.171	Likely Benign	-3.18	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.13	Pathogenic	0.03	Affected			0.1320	0.7186		2	1	0.3	23.04
c.2268G>C	Q756H 2D AIThe SynGAP1 missense variant Q756H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) lean toward a benign interpretation. Thus, the variant is most likely benign based on current computational evidence, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.458154	Structured	0.806299	Binding	0.340	0.866	0.250											-4.625	Likely Benign	0.276	Likely Benign	Likely Benign										0.197	Likely Benign	-2.17	Neutral	0.998	Probably Damaging	0.996	Probably Damaging	1.54	Pathogenic	0.05	Affected			0.1545	0.4404		3	0	0.3	9.01
c.2268G>T	Q756H 2D AIThe SynGAP1 missense variant Q756H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) lean toward a benign interpretation. Thus, the variant is most likely benign based on current computational evidence, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.458154	Structured	0.806299	Binding	0.340	0.866	0.250											-4.625	Likely Benign	0.276	Likely Benign	Likely Benign										0.197	Likely Benign	-2.17	Neutral	0.998	Probably Damaging	0.996	Probably Damaging	1.54	Pathogenic	0.05	Affected			0.1545	0.4404		3	0	0.3	9.01
c.2327G>A	G776D 2D AIThe SynGAP1 missense variant G776D is catalogued in gnomAD (ID 6‑33442485‑G‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from AlphaMissense‑Default, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized scores benign, and the SGM‑Consensus (majority of the four high‑accuracy tools) also indicates benign. Foldetta stability analysis is unavailable, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign effect for G776D, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.377384	Structured	0.886983	Binding	0.296	0.888	0.250								6-33442485-G-A			0.388	Likely Benign	0.566	Likely Pathogenic	Likely Benign										0.188	Likely Benign	0.16	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	4.30	Benign	0.10	Tolerated	3.64	6	0.1835	0.2971		-1	1	-3.1	58.04
c.2363C>A	S788Y 2D AIThe SynGAP1 missense variant S788Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy assessments show that the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect, AlphaMissense‑Optimized is uncertain (treated as unavailable), and Foldetta results are not provided. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.956248	Disordered	0.573557	Binding	0.349	0.895	0.750											-8.745	Likely Pathogenic	0.795	Likely Pathogenic	Ambiguous										0.251	Likely Benign	-4.56	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.0844	0.5551		-3	-2	-0.5	76.10
c.2363C>T	S788F 2D AIThe SynGAP1 missense variant S788F is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; Foldetta stability analysis is unavailable. Overall, the preponderance of predictions points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.956248	Disordered	0.573557	Binding	0.349	0.895	0.750											-7.870	In-Between	0.749	Likely Pathogenic	Likely Benign										0.275	Likely Benign	-4.73	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.0781	0.5824		-3	-2	3.6	60.10
c.2417T>C	F806S 2D AIThe SynGAP1 missense variant F806S is catalogued in gnomAD (ID 6‑33442969‑T‑C) but has no ClinVar entry. Functional prediction tools split into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status because none is reported. Thus, the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.736850	Disordered	0.847454	Binding	0.276	0.904	0.500								6-33442969-T-C	1	6.20e-7	-6.959	Likely Benign	0.911	Likely Pathogenic	Ambiguous										0.269	Likely Benign	-4.13	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.21	Pathogenic	0.00	Affected	3.77	5	0.5067	0.0391	Weaken	-2	-3	-3.6	-60.10
c.2461T>G	C821G 2D AIThe SynGAP1 missense variant C821G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of available predictions (five pathogenic vs. three benign) lean toward pathogenicity. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.745909	Disordered	0.672821	Binding	0.351	0.883	0.750											-4.613	Likely Benign	0.910	Likely Pathogenic	Ambiguous										0.187	Likely Benign	-2.94	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.68	Benign	0.05	Affected			0.3287	0.2747		-3	-3	-2.9	-46.09
c.2467A>C	S823R 2D AIThe SynGAP1 missense variant S823R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all indicate likely pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy prediction tools points to a pathogenic effect for S823R, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-6.612	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.293	Likely Benign	-3.47	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.93	Pathogenic	0.00	Affected			0.0893	0.4046		0	-1	-3.7	69.11
c.2469C>A	S823R 2D AIThe SynGAP1 missense variant S823R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-6.612	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.196	Likely Benign	-3.47	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.93	Pathogenic	0.00	Affected			0.0893	0.4046		0	-1	-3.7	69.11
c.2469C>G	S823R 2D AIThe SynGAP1 missense variant S823R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-6.612	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.196	Likely Benign	-3.47	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.93	Pathogenic	0.00	Affected			0.0893	0.4046		0	-1	-3.7	69.11
c.2470A>C	S824R 2D AIThe SynGAP1 missense variant S824R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome; Foldetta stability analysis is unavailable. Overall, the majority of predictions lean toward a benign interpretation, but the split in high‑accuracy tools introduces uncertainty. The variant is therefore most likely benign, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.611272	Binding	0.314	0.884	0.750											-5.589	Likely Benign	0.996	Likely Pathogenic	Likely Pathogenic										0.131	Likely Benign	-1.67	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.61	Benign	0.23	Tolerated			0.1096	0.4255		0	-1	-3.7	69.11
c.2472C>A	S824R 2D AIThe SynGAP1 missense variant S824R has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM‑Consensus remains benign; Foldetta results are unavailable. Overall, the majority of tools lean toward a benign interpretation, but the presence of a pathogenic prediction from a high‑accuracy model introduces uncertainty. Thus, the variant is most likely benign based on the current predictions, and this assessment does not contradict the ClinVar status, which has no reported classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.611272	Binding	0.314	0.884	0.750											-5.589	Likely Benign	0.996	Likely Pathogenic	Likely Pathogenic										0.154	Likely Benign	-1.67	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.61	Benign	0.23	Tolerated			0.1096	0.4255		0	-1	-3.7	69.11
c.2472C>G	S824R 2D AIThe SynGAP1 missense variant S824R is not reported in ClinVar and has no gnomAD entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus score, which is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN. Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (majority vote) is benign; Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation, as none exists for S824R. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.611272	Binding	0.314	0.884	0.750											-5.589	Likely Benign	0.996	Likely Pathogenic	Likely Pathogenic										0.154	Likely Benign	-1.67	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.61	Benign	0.23	Tolerated			0.1096	0.4255		0	-1	-3.7	69.11
c.2473T>C	S825P 2D AIThe SynGAP1 missense variant S825P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that S825P is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.675549	Disordered	0.618614	Binding	0.384	0.886	0.750											-3.227	Likely Benign	0.959	Likely Pathogenic	Likely Pathogenic										0.285	Likely Benign	-3.12	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.94	Pathogenic	0.02	Affected			0.2060	0.5998		1	-1	-0.8	10.04
c.2479A>T	I827F 2D AIThe SynGAP1 missense variant I827F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The AlphaMissense‑Default score is uncertain, and no Foldetta stability assessment is available. High‑accuracy methods give a benign consensus: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign, with no Foldetta data. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.590140	Disordered	0.636272	Binding	0.383	0.884	0.625											-4.799	Likely Benign	0.517	Ambiguous	Likely Benign										0.155	Likely Benign	-1.30	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.65	Benign	0.09	Tolerated			0.0490	0.2306		1	0	-1.7	34.02
c.2480T>G	I827S 2D AIThe SynGAP1 missense variant I827S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Benign, and AlphaMissense‑Optimized is classified as Uncertain. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.590140	Disordered	0.636272	Binding	0.383	0.884	0.625											-3.693	Likely Benign	0.849	Likely Pathogenic	Ambiguous										0.140	Likely Benign	-0.42	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.70	Benign	0.29	Tolerated			0.2891	0.0512		-1	-2	-5.3	-26.08
c.2533G>A	D845N 2D AIThe SynGAP1 missense variant D845N is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. When the high‑accuracy consensus is considered, AlphaMissense‑Optimized remains pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates pathogenicity. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a pathogenic effect, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.599971	Binding	0.297	0.827	0.500											-6.586	Likely Benign	0.961	Likely Pathogenic	Likely Pathogenic										0.264	Likely Benign	-3.42	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	1.96	Pathogenic	0.00	Affected			0.1216	0.7112		2	1	0.0	-0.98
c.2534A>G	D845G 2D AIThe SynGAP1 missense variant D845G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL classifies it as benign, whereas the remaining 11 predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a Likely Pathogenic status; Foldetta results are not available. Taken together, the preponderance of evidence indicates that D845G is most likely pathogenic, and this assessment does not conflict with the current ClinVar record, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.599971	Binding	0.297	0.827	0.500											-8.209	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic										0.399	Likely Benign	-4.96	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	2.06	Pathogenic	0.00	Affected			0.3953	0.6740		1	-1	3.1	-58.04
c.2569A>T	S857C 2D AIThe SynGAP1 missense variant S857C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the majority of predictions and the high‑accuracy consensus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.475747	Uncertain	0.288	0.826	0.375											-6.335	Likely Benign	0.109	Likely Benign	Likely Benign										0.146	Likely Benign	-1.28	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	4.02	Benign	0.08	Tolerated			0.1221	0.6672		0	-1	3.3	16.06
c.2576G>T	S859I 2D AIThe SynGAP1 missense variant S859I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors a benign outcome. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of computational evidence indicates a benign impact, and this conclusion does not contradict any ClinVar annotation because no ClinVar record exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.648219	Disordered	0.497075	Uncertain	0.288	0.819	0.375											-8.342	Likely Pathogenic	0.351	Ambiguous	Likely Benign										0.256	Likely Benign	-1.94	Neutral	0.997	Probably Damaging	0.996	Probably Damaging	3.99	Benign	0.02	Affected			0.1094	0.5867		-1	-2	5.3	26.08
c.2599G>T	G867W 2D AIThe SynGAP1 missense variant G867W is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.517562	Disordered	0.657954	Binding	0.285	0.801	0.250											-8.983	Likely Pathogenic	0.776	Likely Pathogenic	Likely Benign										0.163	Likely Benign	-2.95	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.64	Benign	0.01	Affected			0.0726	0.4584		-7	-2	-0.5	129.16
c.2618G>T	S873I 2D AIThe SynGAP1 missense variant S873I has no ClinVar record and is not reported in gnomAD. Functional prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the majority of other in‑silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) indicate a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized returns an uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available prediction for this residue. High‑accuracy assessment therefore points to a Likely Pathogenic status from SGM‑Consensus, with AlphaMissense‑Optimized inconclusive and Foldetta missing. Overall, the preponderance of evidence suggests the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.414856	Structured	0.649816	Binding	0.283	0.866	0.125											-9.412	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous										0.305	Likely Benign	-3.44	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	2.66	Benign	0.02	Affected			0.1012	0.5560		-1	-2	5.3	26.08
c.2684G>T	S895I 2D AIThe SynGAP1 missense variant S895I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors a benign outcome; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for S895I, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.788093	Disordered	0.414977	Uncertain	0.294	0.925	0.750											-6.315	Likely Benign	0.697	Likely Pathogenic	Likely Benign										0.144	Likely Benign	-2.34	Neutral	0.997	Probably Damaging	0.996	Probably Damaging	2.65	Benign	0.04	Affected			0.1010	0.6248		-1	-2	5.3	26.08
c.2776T>C	S926P 2D AIThe SynGAP1 missense variant S926P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (benign), FATHMM (pathogenic), and PROVEAN (pathogenic), yielding a Likely Pathogenic classification. AlphaMissense‑Optimized is uncertain, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for S926P. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.461924	Structured	0.981753	Binding	0.295	0.854	0.250											-3.873	Likely Benign	0.916	Likely Pathogenic	Ambiguous										0.424	Likely Benign	-3.79	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.51	Pathogenic	0.00	Affected			0.1738	0.5058		1	-1	-0.8	10.04
c.2780T>C	F927S 2D AIThe SynGAP1 missense variant F927S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome (3 pathogenic vs. 1 benign). AlphaMissense‑Optimized alone predicts pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Based on the preponderance of pathogenic predictions—including the high‑accuracy consensus—the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.529623	Disordered	0.985043	Binding	0.324	0.854	0.250											-5.480	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.481	Likely Benign	-5.68	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.32	Pathogenic	0.00	Affected			0.4748	0.0591		-3	-2	-3.6	-60.10
c.2784G>C	Q928H 2D AIThe SynGAP1 missense variant Q928H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include REVEL and ESM1b, whereas the majority of tools predict it to be pathogenic: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—agrees on a pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.986260	Binding	0.324	0.852	0.250											-4.358	Likely Benign	0.929	Likely Pathogenic	Ambiguous										0.329	Likely Benign	-3.65	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.54	Pathogenic	0.00	Affected			0.1389	0.4811		3	0	0.3	9.01
c.2784G>T	Q928H 2D AIThe SynGAP1 missense variant Q928H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include REVEL and ESM1b, whereas the majority of tools predict it to be pathogenic: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—agrees on a pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.986260	Binding	0.324	0.852	0.250											-4.358	Likely Benign	0.929	Likely Pathogenic	Ambiguous										0.330	Likely Benign	-3.65	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.54	Pathogenic	0.00	Affected			0.1389	0.4811		3	0	0.3	9.01
c.2787C>A	N929K 2D AIThe SynGAP1 missense variant N929K is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign—REVEL—and pathogenic—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status; Foldetta results are not available. Taken together, the preponderance of evidence supports a pathogenic interpretation for N929K, and this conclusion is consistent with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.986867	Binding	0.321	0.851	0.375											-10.041	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.182	Likely Benign	-4.35	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.48	Pathogenic	0.00	Affected			0.2098	0.6046		1	0	-0.4	14.07
c.2787C>G	N929K 2D AIThe SynGAP1 missense variant N929K is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign—REVEL—and pathogenic—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status; Foldetta results are not available. Taken together, the preponderance of evidence supports a pathogenic interpretation for N929K, and this conclusion is consistent with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.986867	Binding	0.321	0.851	0.375											-10.041	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.182	Likely Benign	-4.35	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.48	Pathogenic	0.00	Affected			0.2098	0.6046		1	0	-0.4	14.07
c.2795T>C	F932S 2D AIThe SynGAP1 missense variant F932S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic effect: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. ESM1b is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from multiple prediction algorithms and high‑accuracy tools indicates that F932S is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.675549	Disordered	0.989197	Binding	0.293	0.858	0.500											-7.196	In-Between	0.993	Likely Pathogenic	Likely Pathogenic										0.260	Likely Benign	-4.45	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.31	Pathogenic	0.00	Affected			0.4257	0.0584		-3	-2	-3.6	-60.10
c.2798A>T	H933L 2D AIThe SynGAP1 H933L missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.666105	Disordered	0.987531	Binding	0.305	0.862	0.625											-0.858	Likely Benign	0.470	Ambiguous	Likely Benign										0.388	Likely Benign	-6.26	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.38	Pathogenic	0.02	Affected			0.1003	0.5749		-2	-3	7.0	-23.98
c.2799C>A	H933Q 2D AIThe SynGAP1 missense variant H933Q has no ClinVar record and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to benign (two benign versus one pathogenic vote). High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus as benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) is unavailable for this variant. Overall, the preponderance of evidence points to a benign impact, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.666105	Disordered	0.987531	Binding	0.305	0.862	0.625											-3.042	Likely Benign	0.410	Ambiguous	Likely Benign										0.211	Likely Benign	-2.98	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.54	Benign	0.53	Tolerated			0.1654	0.3938		3	0	-0.3	-9.01
c.2799C>G	H933Q 2D AIThe SynGAP1 H933Q missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction between the predictions and ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.666105	Disordered	0.987531	Binding	0.305	0.862	0.625											-3.042	Likely Benign	0.410	Ambiguous	Likely Benign										0.210	Likely Benign	-2.98	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.54	Benign	0.53	Tolerated			0.1654	0.3938		3	0	-0.3	-9.01
c.2803G>T	A935S 2D AIThe SynGAP1 missense variant A935S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the overall assessment. Overall, the majority of evidence points to a benign effect for A935S, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.736850	Disordered	0.980490	Binding	0.286	0.865	0.625											-3.361	Likely Benign	0.139	Likely Benign	Likely Benign										0.167	Likely Benign	-0.60	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.53	Benign	0.00	Affected			0.2719	0.5496		1	1	-2.6	16.00
c.2804C>G	A935G 2D AIThe SynGAP1 missense variant A935G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) lean toward a benign interpretation. Thus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.736850	Disordered	0.980490	Binding	0.286	0.865	0.625											-2.868	Likely Benign	0.179	Likely Benign	Likely Benign										0.152	Likely Benign	-1.97	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.32	Pathogenic	0.00	Affected			0.2318	0.4679		1	0	-2.2	-14.03
c.2804C>T	A935V 2D AIThe SynGAP1 missense variant A935V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also leans benign (2 benign vs. 1 pathogenic votes). Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for A935V, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.736850	Disordered	0.980490	Binding	0.286	0.865	0.625											-4.750	Likely Benign	0.397	Ambiguous	Likely Benign										0.194	Likely Benign	-2.06	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.30	Pathogenic	0.00	Affected			0.1340	0.5941		0	0	2.4	28.05
c.2948G>T	S983I 2D AIThe SynGAP1 missense variant S983I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). In silico predictors that agree on a benign effect are REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (3 pathogenic vs. 1 benign) is likely pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence indicates that S983I is most likely pathogenic, and this conclusion is not contradicted by the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.707965	Disordered	0.960212	Binding	0.277	0.889	0.625											-6.259	Likely Benign	0.968	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-2.67	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	2.02	Pathogenic	0.00	Affected			0.1380	0.4625		-1	-2	5.3	26.08
c.2954G>T	S985I 2D AIThe SynGAP1 missense variant S985I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. ESM1b remains uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic verdict (2 pathogenic vs. 1 benign). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates that S985I is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.720929	Disordered	0.941547	Binding	0.302	0.896	0.750											-7.858	In-Between	0.971	Likely Pathogenic	Likely Pathogenic										0.131	Likely Benign	-2.78	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	2.50	Benign	0.00	Affected			0.1367	0.5206		-1	-2	5.3	26.08
c.3007A>C	S1003R 2D AIThe SynGAP1 missense variant S1003R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of evaluated tools (six pathogenic vs. three benign) indicate a pathogenic impact. This prediction aligns with the lack of ClinVar annotation and does not contradict any existing clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.834292	Disordered	0.947349	Binding	0.272	0.901	0.625											-5.113	Likely Benign	0.991	Likely Pathogenic	Likely Pathogenic										0.110	Likely Benign	-1.88	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.48	Pathogenic	0.00	Affected	3.77	5	0.1151	0.3746		0	-1	-3.7	69.11
c.3009C>A	S1003R 2D AIThe SynGAP1 missense variant S1003R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of evaluated tools (six pathogenic vs. three benign) indicate a pathogenic impact. This prediction aligns with the lack of ClinVar annotation and does not contradict any existing clinical classification. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.834292	Disordered	0.947349	Binding	0.272	0.901	0.625											-5.113	Likely Benign	0.991	Likely Pathogenic	Likely Pathogenic										0.141	Likely Benign	-1.88	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.48	Pathogenic	0.00	Affected	3.77	5	0.1151	0.3746		0	-1	-3.7	69.11
c.3009C>G	S1003R 2D AIThe SynGAP1 missense variant S1003R (ClinVar ID 1798770.0) is listed as Uncertain in ClinVar and is not present in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and ESM1b, while pathogenic predictions are reported by polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessment shows AlphaMissense‑Optimized classifying the variant as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign, two pathogenic), and Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a pathogenic effect, which contrasts with the ClinVar designation of Uncertain. Thus, the variant is most likely pathogenic, contradicting the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.834292	Disordered	0.947349	Binding	0.272	0.901	0.625					Uncertain		1				-5.113	Likely Benign	0.991	Likely Pathogenic	Likely Pathogenic										0.141	Likely Benign	-1.88	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.48	Pathogenic	0.00	Affected	3.77	5	0.1151	0.3746		0	-1	-3.7	69.11
c.3011A>T	H1004L 2D AIThe SynGAP1 missense variant H1004L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (a majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (two pathogenic vs two benign votes). Foldetta, which would provide a protein‑folding stability estimate, has no available result for this variant. Overall, the balance of evidence leans toward a benign interpretation, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.808535	Disordered	0.943707	Binding	0.271	0.901	0.750											-5.179	Likely Benign	0.716	Likely Pathogenic	Likely Benign										0.220	Likely Benign	-3.14	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.75	Benign	0.55	Tolerated			0.1223	0.6026		-2	-3	7.0	-23.98
c.3012C>A	H1004Q 2D AIThe SynGAP1 missense variant H1004Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.808535	Disordered	0.943707	Binding	0.271	0.901	0.750											-3.872	Likely Benign	0.853	Likely Pathogenic	Ambiguous										0.126	Likely Benign	-1.55	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.78	Benign	0.71	Tolerated	3.77	5	0.1831	0.3832		0	3	-0.3	-9.01
c.3012C>G	H1004Q 2D AIThe SynGAP1 missense variant H1004Q is catalogued in gnomAD (ID 6‑33443564‑C‑G) but has no ClinVar entry. Functional prediction tools that agree on benign impact include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while PolyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default predict pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” SGM‑Consensus as “Likely Benign,” and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Taken together, the preponderance of evidence (six benign predictions versus three pathogenic) indicates that H1004Q is most likely benign. This conclusion does not contradict ClinVar status, as the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.808535	Disordered	0.943707	Binding	0.271	0.901	0.750								6-33443564-C-G	3	1.86e-6	-3.872	Likely Benign	0.853	Likely Pathogenic	Ambiguous										0.126	Likely Benign	-1.55	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.78	Benign	0.71	Tolerated	3.77	5	0.1831	0.3832		0	3	-0.3	-9.01
c.3013A>C	S1005R 2D AIThe SynGAP1 missense variant S1005R has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign calls from REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign); pathogenic calls from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicting pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Benign. Foldetta stability analysis is unavailable. Overall, the evidence is split, with an equal number of benign and pathogenic predictions and no ClinVar status to contradict. Thus, the variant is most likely pathogenic based on the majority of high‑confidence tools, and this assessment is not contradicted by ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.812494	Disordered	0.936602	Binding	0.261	0.897	0.750											-3.300	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.135	Likely Benign	-2.29	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.66	Benign	0.00	Affected	3.77	5	0.0994	0.2856		-1	0	-3.7	69.11
c.3015C>A	S1005R 2D AISynGAP1 missense variant S1005R has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign); pathogenic predictions include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains benign; Foldetta stability analysis is unavailable. The overall evidence is split, with five tools favoring benign and five favoring pathogenic, and the two high‑accuracy methods disagree. Consequently, the variant’s impact is uncertain; it is not contradicted by any ClinVar status because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.812494	Disordered	0.936602	Binding	0.261	0.897	0.750											-3.300	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.165	Likely Benign	-2.29	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.66	Benign	0.00	Affected	3.77	5	0.0994	0.2856		-1	0	-3.7	69.11
c.3015C>G	S1005R 2D AIThe SynGAP1 missense variant S1005R is catalogued in gnomAD (ID 6‑33443567‑C‑G) but has no ClinVar entry. Prediction tools cluster into two groups: benign calls include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, and FATHMM; pathogenic calls include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts pathogenic, while the SGM consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the predictions are split, with an equal number of benign and pathogenic calls and a mixed outcome from the high‑accuracy tools. Consequently, the variant is most likely of uncertain significance; there is no contradiction with ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.812494	Disordered	0.936602	Binding	0.261	0.897	0.750								6-33443567-C-G	2	1.24e-6	-3.300	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.165	Likely Benign	-2.29	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.66	Benign	0.00	Affected	3.77	5	0.0994	0.2856		-1	0	-3.7	69.11
c.3019A>C	S1007R 2D AIThe SynGAP1 missense variant S1007R is not reported in ClinVar and has no gnomAD entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give opposing results: AlphaMissense‑Optimized classifies the variant as pathogenic, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the predictions are split, with an equal number of benign and pathogenic calls, and the high‑accuracy tools disagree. Thus, the variant is most likely pathogenic based on the majority of predictions, and this assessment does not contradict ClinVar status, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.925648	Binding	0.295	0.899	0.750											-5.441	Likely Benign	0.982	Likely Pathogenic	Likely Pathogenic										0.211	Likely Benign	-1.93	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.65	Benign	0.01	Affected			0.1121	0.3237		0	-1	-3.7	69.11
c.3021T>A	S1007R 2D AIThe SynGAP1 missense variant S1007R has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign); pathogenic predictions include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, whereas the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the evidence leans toward a pathogenic interpretation, with no ClinVar status to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.925648	Binding	0.295	0.899	0.750											-5.441	Likely Benign	0.982	Likely Pathogenic	Likely Pathogenic										0.219	Likely Benign	-1.93	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.65	Benign	0.01	Affected			0.1121	0.3237		0	-1	-3.7	69.11
c.3021T>G	S1007R 2D AISynGAP1 missense variant S1007R has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, while the SGM‑Consensus (a majority vote of four high‑accuracy predictors) indicates a likely benign outcome; Foldetta results are unavailable. Overall, the evidence is split, with an equal number of benign and pathogenic predictions. The variant is most likely pathogenic based on the presence of several high‑confidence pathogenic calls, and this assessment does not contradict ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.925648	Binding	0.295	0.899	0.750											-5.441	Likely Benign	0.982	Likely Pathogenic	Likely Pathogenic										0.219	Likely Benign	-1.93	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.65	Benign	0.01	Affected			0.1121	0.3237		0	-1	-3.7	69.11
c.3227T>G	L1076W 2D AIThe SynGAP1 missense variant L1076W is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evaluated predictors (five pathogenic vs. three benign) lean toward a pathogenic interpretation. This prediction is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.922952	Disordered	0.989617	Binding	0.301	0.892	0.750											-6.377	Likely Benign	0.822	Likely Pathogenic	Ambiguous										0.183	Likely Benign	-1.40	Neutral	1.000	Probably Damaging	0.996	Probably Damaging	2.38	Pathogenic	0.02	Affected			0.0749	0.3740		-2	-2	-4.7	73.05
c.3253C>T	R1085W 2D AISynGAP1 missense variant R1085W is listed in ClinVar as Uncertain and is present in gnomAD (ID 6‑33443805‑C‑T). Prediction tools that classify the variant as benign include REVEL, ESM1b, and FATHMM, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is Uncertain, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta stability assessment are unavailable. Overall, the majority of available predictions (five pathogenic vs. three benign) indicate a pathogenic effect. Thus, the variant is most likely pathogenic, which contradicts the ClinVar designation of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.852992	Disordered	0.978838	Binding	0.270	0.888	1.000					Uncertain		1	6-33443805-C-T	2	1.26e-6	-6.339	Likely Benign	0.821	Likely Pathogenic	Ambiguous										0.202	Likely Benign	-3.15	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.70	Benign	0.00	Affected	3.77	5	0.1238	0.3700		-3	2	3.6	30.03
c.3256C>G	P1086A 2D AIThe SynGAP1 missense variant P1086A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors benign, and Foldetta data are unavailable. Taken together, the balance of evidence points to a benign effect for P1086A. This conclusion does not conflict with the ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.849326	Disordered	0.977190	Binding	0.393	0.885	1.000											-4.317	Likely Benign	0.372	Ambiguous	Likely Benign										0.206	Likely Benign	-2.98	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.78	Benign	0.00	Affected			0.3084	0.4463		1	-1	3.4	-26.04
c.3262A>C	S1088R 2D AIThe SynGAP1 missense variant S1088R is not reported in ClinVar and has no gnomAD entry. Prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, and FATHMM, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves as Likely Benign, reflecting the majority of benign calls. High‑accuracy assessments further support this: AlphaMissense‑Optimized labels the variant as Pathogenic, but the SGM‑Consensus (majority vote) remains Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence leans toward a benign effect; this conclusion does not conflict with ClinVar, which contains no entry for S1088R. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.910643	Disordered	0.975261	Binding	0.336	0.889	1.000											-4.588	Likely Benign	0.988	Likely Pathogenic	Likely Pathogenic										0.209	Likely Benign	-1.96	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.72	Benign	0.01	Affected	3.77	5	0.1190	0.4502		-1	0	-3.7	69.11
c.3262A>T	S1088C 2D AIThe SynGAP1 missense variant S1088C is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar) and SIFT. Two tools, AlphaMissense‑Default and ESM1b, return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it contains two benign and two uncertain calls, and Foldetta data are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.910643	Disordered	0.975261	Binding	0.336	0.889	1.000											-7.532	In-Between	0.547	Ambiguous	Likely Benign										0.212	Likely Benign	-2.33	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.59	Benign	0.01	Affected			0.1571	0.6166		0	-1	3.3	16.06
c.3264C>A	S1088R 2D AIThe SynGAP1 missense variant S1088R is not reported in ClinVar and is present in gnomAD (ID 6‑33443816‑C‑A). Prediction tools that classify the variant as benign include REVEL, PROVEAN, ESM1b, and FATHMM, whereas polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized predict it to be pathogenic. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains benign; Foldetta results are unavailable. Overall, the balance of evidence—five pathogenic versus four benign predictions—suggests the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for S1088R. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.910643	Disordered	0.975261	Binding	0.336	0.889	1.000								6-33443816-C-A			-4.588	Likely Benign	0.988	Likely Pathogenic	Likely Pathogenic										0.181	Likely Benign	-1.96	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.72	Benign	0.01	Affected	3.77	5	0.1190	0.4502		-1	0	-3.7	69.11
c.3264C>G	S1088R 2D AIThe SynGAP1 missense variant S1088R has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, whereas the SGM‑Consensus remains Benign; Foldetta results are unavailable. Overall, the balance of evidence slightly favors a pathogenic interpretation, with no conflict with ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.910643	Disordered	0.975261	Binding	0.336	0.889	1.000											-4.588	Likely Benign	0.988	Likely Pathogenic	Likely Pathogenic										0.181	Likely Benign	-1.96	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.72	Benign	0.01	Affected	3.77	5	0.1190	0.4502		-1	0	-3.7	69.11
c.3413C>A	S1138Y 2D AIThe SynGAP1 missense variant S1138Y is listed in ClinVar with an “Uncertain” significance and is present in gnomAD (ID 6‑33444448‑C‑A). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. High‑accuracy predictions from AlphaMissense‑Optimized and the SGM Consensus both indicate a benign outcome, while Foldetta data are missing. Overall, the balance of evidence—especially from the high‑accuracy tools—suggests that the variant is most likely benign. This benign prediction does not contradict the ClinVar status, which remains uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.891961	Disordered	0.738250	Binding	0.346	0.869	1.000					Uncertain		1	6-33444448-C-A	3	1.86e-6	-6.610	Likely Benign	0.449	Ambiguous	Likely Benign										0.391	Likely Benign	-2.51	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	5.41	Benign	0.05	Affected	4.32	4	0.1034	0.5449		-2	-3	-0.5	76.10
c.3413C>T	S1138F 2D AIThe SynGAP1 missense variant S1138F is not reported in ClinVar and is present in gnomAD (ID 6‑33444448‑C‑T). Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. The high‑accuracy AlphaMissense‑Optimized score is benign. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default (uncertain), ESM1b (benign), FATHMM (benign), and PROVEAN (pathogenic), resolves to benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of available predictions indicates a benign effect. This conclusion is consistent with the absence of a ClinVar classification, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.891961	Disordered	0.738250	Binding	0.346	0.869	1.000								6-33444448-C-T	1	6.20e-7	-6.298	Likely Benign	0.379	Ambiguous	Likely Benign										0.407	Likely Benign	-2.88	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	5.42	Benign	0.03	Affected	4.32	4	0.0991	0.5623		-2	-3	3.6	60.10
c.3466G>A	A1156T 2D AIThe SynGAP1 missense variant A1156T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence from multiple in silico tools points to a pathogenic effect for A1156T, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.720929	Disordered	0.871395	Binding	0.294	0.861	0.500											-3.732	Likely Benign	0.988	Likely Pathogenic	Likely Pathogenic										0.285	Likely Benign	-2.99	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	1.63	Pathogenic	0.00	Affected			0.1366	0.7442		1	0	-2.5	30.03
c.3476C>A	S1159Y 2D AIThe SynGAP1 missense variant S1159Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome; Foldetta results are unavailable. Overall, the majority of evidence (six benign predictions versus five pathogenic, plus a benign consensus) points to a likely benign impact for S1159Y. This conclusion does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.626927	Disordered	0.867068	Binding	0.343	0.846	0.375											-5.665	Likely Benign	0.957	Likely Pathogenic	Likely Pathogenic										0.195	Likely Benign	-1.57	Neutral	0.997	Probably Damaging	0.996	Probably Damaging	2.65	Benign	0.07	Tolerated			0.0567	0.4923		-3	-2	-0.5	76.10
c.3476C>T	S1159F 2D AIThe SynGAP1 missense variant S1159F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) remains benign; Foldetta stability analysis is unavailable. Overall, the balance of evidence leans toward a benign interpretation, and this conclusion does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.626927	Disordered	0.867068	Binding	0.343	0.846	0.375											-5.627	Likely Benign	0.976	Likely Pathogenic	Likely Pathogenic										0.181	Likely Benign	-1.11	Neutral	0.997	Probably Damaging	0.996	Probably Damaging	2.66	Benign	0.20	Tolerated			0.0527	0.5211		-3	-2	3.6	60.10
c.3488A>C	H1163P 2D AIThe SynGAP1 missense variant H1163P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are SIFT, ESM1b, and FATHMM, while those that agree on a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a tie (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, more tools predict pathogenicity than benignity (5 vs. 3), and there is no ClinVar record to contradict this assessment. Thus, the variant is most likely pathogenic based on the available predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.509769	Disordered	0.858469	Binding	0.328	0.825	0.375											-2.023	Likely Benign	0.815	Likely Pathogenic	Ambiguous										0.578	Likely Pathogenic	-3.19	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	5.39	Benign	0.10	Tolerated			0.2015	0.3900		0	-2	1.6	-40.02
c.3562G>A	D1188N 2D AIThe SynGAP1 D1188N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the balance of evidence favors a pathogenic classification for D1188N, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.476583	Structured	0.484322	Uncertain	0.687	0.626	0.625											-5.621	Likely Benign	0.962	Likely Pathogenic	Likely Pathogenic										0.340	Likely Benign	-2.50	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	5.47	Benign	0.00	Affected			0.0767	0.4663		2	1	0.0	-0.98
c.3563A>G	D1188G 2D AIThe SynGAP1 D1188G missense change is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus method SGM, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a tie and is therefore inconclusive. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not conflict with any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.476583	Structured	0.484322	Uncertain	0.687	0.626	0.625											-5.286	Likely Benign	0.981	Likely Pathogenic	Likely Pathogenic										0.440	Likely Benign	-3.69	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	5.47	Benign	0.00	Affected			0.2771	0.4880		1	-1	3.1	-58.04
c.3569G>T	S1190I 2D AIThe SynGAP1 missense change S1190I is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM. Those that predict a pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized model classifies the variant as pathogenic, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Benign. Foldetta stability analysis is unavailable. Overall, the balance of evidence favors a pathogenic interpretation, and this assessment does not contradict any ClinVar annotation because no ClinVar record exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.575842	Disordered	0.455760	Uncertain	0.742	0.624	0.625											-4.842	Likely Benign	0.958	Likely Pathogenic	Likely Pathogenic										0.371	Likely Benign	-1.89	Neutral	0.997	Probably Damaging	0.996	Probably Damaging	5.26	Benign	0.04	Affected			0.0881	0.4175		-1	-2	5.3	26.08
c.3589G>C	E1197Q 2D AIThe SynGAP1 missense variant E1197Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as benign, and no Foldetta stability data are available. Overall, the balance of evidence favors a benign interpretation, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.613573	Disordered	0.437361	Uncertain	0.827	0.599	0.250											-2.771	Likely Benign	0.692	Likely Pathogenic	Likely Benign										0.304	Likely Benign	-0.60	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	5.44	Benign	0.29	Tolerated			0.0690	0.5265		2	2	0.0	-0.98
c.3590A>G	E1197G 2D AIThe SynGAP1 missense variant E1197G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are ESM1b and FATHMM, while six tools—REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default—consistently predict a pathogenic impact. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie and therefore unavailable; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, has no reported result. Overall, the preponderance of evidence (six pathogenic vs. two benign predictions) indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.613573	Disordered	0.437361	Uncertain	0.827	0.599	0.250											-6.015	Likely Benign	0.807	Likely Pathogenic	Ambiguous										0.504	Likely Pathogenic	-3.46	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	5.38	Benign	0.05	Affected			0.2593	0.4894		0	-2	3.1	-72.06
c.3596A>G	E1199G 2D AIThe SynGAP1 missense change E1199G is not reported in ClinVar (ClinVar ID = None) and has no entries in gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, while the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for E1199G, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.538167	Disordered	0.444533	Uncertain	0.878	0.598	0.250											-13.414	Likely Pathogenic	0.947	Likely Pathogenic	Ambiguous										0.360	Likely Benign	-5.08	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.45	Pathogenic	0.00	Affected			0.2461	0.3960		0	-2	3.1	-72.06
c.3601G>C	E1201Q 2D AIThe SynGAP1 E1201Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas tools that agree on a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of evaluated predictors (six pathogenic vs. three benign) indicate a pathogenic impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.525368	Disordered	0.481868	Uncertain	0.870	0.596	0.250											-4.415	Likely Benign	0.967	Likely Pathogenic	Likely Pathogenic										0.264	Likely Benign	-2.44	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	1.62	Pathogenic	0.03	Affected			0.0769	0.5473		2	2	0.0	-0.98
c.3602A>G	E1201G 2D AIThe SynGAP1 missense variant E1201G is not reported in ClinVar and has no entry in gnomAD. Prediction tools that assess the variant’s effect fall into two groups: the single benign prediction comes from REVEL, whereas all other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—classify it as pathogenic. The SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) confirms pathogenicity. No Foldetta stability analysis is available, so it does not influence the conclusion. Overall, the preponderance of evidence points to the variant being most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.525368	Disordered	0.481868	Uncertain	0.870	0.596	0.250											-13.190	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic										0.382	Likely Benign	-5.31	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.61	Pathogenic	0.01	Affected			0.2632	0.5099		0	-2	3.1	-72.06
c.3604A>T	I1202F 2D AIThe SynGAP1 missense variant I1202F is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) is likely pathogenic. Foldetta results are unavailable. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.510422	Binding	0.874	0.593	0.250											-12.304	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.188	Likely Benign	-3.23	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.81	Pathogenic	0.02	Affected			0.0583	0.2079		1	0	-1.7	34.02
c.3605T>G	I1202S 2D AIThe SynGAP1 missense variant I1202S is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are not available. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.510422	Binding	0.874	0.593	0.250											-11.877	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.431	Likely Benign	-4.68	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.80	Pathogenic	0.00	Affected			0.3021	0.0640		-1	-2	-5.3	-26.08
c.3634T>C	S1212P 2D AIThe SynGAP1 missense variant S1212P is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Prediction tools that classify the variant as benign include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict it to be pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic effect. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus likewise reports likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of computational evidence points to the variant being most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.566480	Disordered	0.548409	Binding	0.852	0.565	0.500											-13.336	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.239	Likely Benign	-3.79	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.05	Pathogenic	0.00	Affected			0.1585	0.4370		1	-1	-0.8	10.04
c.3649G>C	E1217Q 2D AIThe SynGAP1 missense variant E1217Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of tools (five pathogenic vs. three benign) and the SGM Consensus support a pathogenic classification, which does not contradict the lack of ClinVar annotation. Thus, the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.599170	Disordered	0.493043	Uncertain	0.877	0.563	0.250											-8.887	Likely Pathogenic	0.398	Ambiguous	Likely Benign										0.219	Likely Benign	-2.16	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.38	Pathogenic	0.00	Affected			0.0949	0.4745		2	2	0.0	-0.98
c.3650A>G	E1217G 2D AIThe SynGAP1 missense variant E1217G is reported in gnomAD (ID 6‑33446642‑A‑G) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) all predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for E1217G. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.599170	Disordered	0.493043	Uncertain	0.877	0.563	0.250								6-33446642-A-G			-10.803	Likely Pathogenic	0.620	Likely Pathogenic	Likely Benign										0.331	Likely Benign	-5.38	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.35	Pathogenic	0.00	Affected	3.77	5	0.2205	0.4927		-2	0	3.1	-72.06
c.3652G>C	E1218Q 2D AIThe SynGAP1 E1218Q missense change is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and ESM1b, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments are less decisive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie and thus inconclusive; Foldetta results are not available. Consequently, the majority of conventional predictors lean toward pathogenicity, but the most reliable tools do not provide a clear verdict. The variant is therefore most likely pathogenic based on the available predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.595080	Disordered	0.483050	Uncertain	0.898	0.565	0.375											-6.490	Likely Benign	0.857	Likely Pathogenic	Ambiguous										0.226	Likely Benign	-2.09	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.32	Pathogenic	0.00	Affected			0.0784	0.3666		2	2	0.0	-0.98
c.3653A>G	E1218G 2D AIThe SynGAP1 missense variant E1218G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as likely pathogenic. AlphaMissense‑Optimized returns an uncertain result, and no Foldetta (FoldX‑MD/Rosetta) stability assessment is available. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant has not been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.483050	Uncertain	0.898	0.565	0.375											-5.595	Likely Benign	0.864	Likely Pathogenic	Ambiguous										0.413	Likely Benign	-5.61	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.22	Pathogenic	0.00	Affected			0.2496	0.4095		0	-2	3.1	-72.06
c.3658G>C	E1220Q 2D AIThe SynGAP1 missense variant E1220Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta data are unavailable. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.703578	Disordered	0.444845	Uncertain	0.881	0.551	0.375											-12.066	Likely Pathogenic	0.846	Likely Pathogenic	Ambiguous										0.276	Likely Benign	-2.59	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.62	Pathogenic	0.00	Affected			0.0896	0.3997		2	2	0.0	-0.98
c.3659A>G	E1220G 2D AIThe SynGAP1 missense variant E1220G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign change, whereas all other evaluated algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence indicates that E1220G is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.703578	Disordered	0.444845	Uncertain	0.881	0.551	0.375											-12.121	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic										0.454	Likely Benign	-6.05	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.61	Pathogenic	0.00	Affected			0.2791	0.4030		0	-2	3.1	-72.06
c.3678G>C	Q1226H 2D AIThe SynGAP1 missense variant Q1226H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic impact. AlphaMissense‑Optimized is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the collective evidence, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as no ClinVar entry exists for Q1226H. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.432206	Uncertain	0.850	0.547	0.250											-8.363	Likely Pathogenic	0.954	Likely Pathogenic	Ambiguous										0.241	Likely Benign	-3.62	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.75	Pathogenic	0.00	Affected			0.0913	0.3230		3	0	0.3	9.01
c.3678G>T	Q1226H 2D AIThe SynGAP1 missense variant Q1226H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic impact. AlphaMissense‑Optimized is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the collective evidence, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as no ClinVar entry exists for Q1226H. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.432206	Uncertain	0.850	0.547	0.250											-8.363	Likely Pathogenic	0.954	Likely Pathogenic	Ambiguous										0.241	Likely Benign	-3.62	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.75	Pathogenic	0.00	Affected			0.0913	0.3230		3	0	0.3	9.01
c.3679G>C	E1227Q 2D AIThe SynGAP1 missense variant E1227Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and PROVEAN, whereas a majority of tools predict a pathogenic impact: polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, while the SGM‑Consensus remains pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple in silico predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.513880	Disordered	0.433399	Uncertain	0.860	0.544	0.500											-9.212	Likely Pathogenic	0.860	Likely Pathogenic	Ambiguous										0.277	Likely Benign	-2.28	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.30	Pathogenic	0.00	Affected			0.0761	0.6204		2	2	0.0	-0.98
c.3680A>G	E1227G 2D AIThe SynGAP1 missense variant E1227G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. AlphaMissense‑Optimized yields an uncertain result, and Foldetta (FoldX‑MD/Rosetta stability analysis) is not available for this variant. Overall, the preponderance of evidence from high‑accuracy predictors and consensus methods indicates that E1227G is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.513880	Disordered	0.433399	Uncertain	0.860	0.544	0.500											-9.328	Likely Pathogenic	0.903	Likely Pathogenic	Ambiguous										0.336	Likely Benign	-5.26	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.28	Pathogenic	0.00	Affected			0.2725	0.5550		0	-2	3.1	-72.06
c.3687A>C	Q1229H 2D AIThe SynGAP1 missense variant Q1229H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta results are unavailable. Overall, the majority of evaluated predictors (five out of nine) indicate a pathogenic impact, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Thus, the variant is most likely pathogenic based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.490133	Structured	0.466729	Uncertain	0.865	0.544	0.375											-6.215	Likely Benign	0.505	Ambiguous	Likely Benign										0.219	Likely Benign	-3.36	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.75	Pathogenic	0.05	Affected			0.0948	0.2494		3	0	0.3	9.01
c.3687A>T	Q1229H 2D AIThe SynGAP1 missense variant Q1229H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta results are unavailable. Overall, the majority of evaluated predictors (five out of nine) indicate a pathogenic impact, so the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.490133	Structured	0.466729	Uncertain	0.865	0.544	0.375											-6.215	Likely Benign	0.505	Ambiguous	Likely Benign										0.219	Likely Benign	-3.36	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.75	Pathogenic	0.05	Affected			0.0948	0.2494		3	0	0.3	9.01
c.3708G>C	Q1236H 2D AIThe SynGAP1 missense variant Q1236H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. AlphaMissense‑Default is uncertain, and no Foldetta (FoldX‑MD + Rosetta) stability result is available, so it does not contribute evidence. Overall, the majority of high‑accuracy and consensus predictions indicate a benign impact, and this is consistent with the lack of ClinVar annotation. Thus, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.680603	Disordered	0.567914	Binding	0.883	0.537	0.125											-6.670	Likely Benign	0.530	Ambiguous	Likely Benign										0.163	Likely Benign	-2.43	Neutral	0.998	Probably Damaging	0.996	Probably Damaging	2.65	Benign	0.01	Affected			0.0915	0.2213		3	0	0.3	9.01
c.3708G>T	Q1236H 2D AIThe SynGAP1 missense variant Q1236H is not reported in ClinVar and is absent from gnomAD. Functional prediction consensus shows a split: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus, whereas pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar) and SIFT. AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely benign. Foldetta stability analysis is not available. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.680603	Disordered	0.567914	Binding	0.883	0.537	0.125											-6.670	Likely Benign	0.530	Ambiguous	Likely Benign										0.163	Likely Benign	-2.43	Neutral	0.998	Probably Damaging	0.996	Probably Damaging	2.65	Benign	0.01	Affected			0.0915	0.2213		3	0	0.3	9.01
c.3714G>C	Q1238H 2D AIThe SynGAP1 missense variant Q1238H is reported in gnomAD (variant ID 6‑33446706‑G‑C) but has no ClinVar entry. Functional prediction tools split into two groups: benign predictions come from REVEL and AlphaMissense‑Optimized, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar classification (none exists). Thus, based on current predictions, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.562014	Disordered	0.548882	Binding	0.855	0.545	0.250								6-33446706-G-C	1	6.20e-7	-8.647	Likely Pathogenic	0.757	Likely Pathogenic	Likely Benign										0.202	Likely Benign	-3.49	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	2.31	Pathogenic	0.01	Affected	3.77	5	0.1007	0.3004		0	3	0.3	9.01
c.3714G>T	Q1238H 2D AIThe SynGAP1 missense variant Q1238H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the remaining predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) all indicate a pathogenic impact. High‑accuracy assessments further support this dichotomy: AlphaMissense‑Optimized classifies the variant as benign, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it as Likely Pathogenic. No Foldetta stability prediction is available. Overall, the preponderance of evidence from multiple independent tools points to a pathogenic effect for Q1238H. This conclusion is not contradicted by ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.562014	Disordered	0.548882	Binding	0.855	0.545	0.250											-8.647	Likely Pathogenic	0.757	Likely Pathogenic	Likely Benign										0.202	Likely Benign	-3.49	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	2.31	Pathogenic	0.01	Affected	3.77	5	0.1007	0.3004		0	3	0.3	9.01
c.3730A>C	S1244R 2D AIThe SynGAP1 missense variant S1244R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. The SGM‑Consensus, which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as likely pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) confirms a likely pathogenic status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.648219	Disordered	0.411055	Uncertain	0.833	0.549	0.500											-10.986	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.309	Likely Benign	-3.49	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.09	Pathogenic	0.04	Affected			0.0778	0.3098		0	-1	-3.7	69.11
c.3732T>A	S1244R 2D AIThe SynGAP1 missense variant S1244R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.648219	Disordered	0.411055	Uncertain	0.833	0.549	0.500											-10.986	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.274	Likely Benign	-3.49	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.09	Pathogenic	0.04	Affected			0.0778	0.3098		0	-1	-3.7	69.11
c.3732T>G	S1244R 2D AIThe SynGAP1 missense variant S1244R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.648219	Disordered	0.411055	Uncertain	0.833	0.549	0.500											-10.986	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.274	Likely Benign	-3.49	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.09	Pathogenic	0.04	Affected			0.0778	0.3098		0	-1	-3.7	69.11
c.3733G>C	E1245Q 2D AIThe SynGAP1 missense change E1245Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and PROVEAN, whereas pathogenic predictions are made by polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to a likely pathogenic verdict (3 pathogenic vs. 1 benign). High‑accuracy assessments further support this: AlphaMissense‑Optimized is uncertain, SGM‑Consensus is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is not available. Consequently, the majority of evidence points to a pathogenic effect. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.712013	Disordered	0.387847	Uncertain	0.869	0.554	0.625											-11.323	Likely Pathogenic	0.804	Likely Pathogenic	Ambiguous										0.210	Likely Benign	-2.29	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.32	Pathogenic	0.00	Affected			0.0819	0.5952		2	2	0.0	-0.98
c.3734A>G	E1245G 2D AIThe SynGAP1 missense variant E1245G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is classified as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.712013	Disordered	0.387847	Uncertain	0.869	0.554	0.625											-12.113	Likely Pathogenic	0.901	Likely Pathogenic	Ambiguous										0.299	Likely Benign	-5.65	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.22	Pathogenic	0.00	Affected			0.2145	0.5447		0	-2	3.1	-72.06
c.3750G>C	Q1250H 2D AIThe SynGAP1 missense variant Q1250H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the overall assessment. Overall, the majority of evidence points to a benign effect for Q1250H, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.759478	Disordered	0.360484	Uncertain	0.881	0.554	0.750											-4.832	Likely Benign	0.252	Likely Benign	Likely Benign										0.118	Likely Benign	-1.91	Neutral	0.998	Probably Damaging	0.996	Probably Damaging	2.64	Benign	0.02	Affected			0.1084	0.2139		3	0	0.3	9.01
c.3750G>T	Q1250H 2D AIThe SynGAP1 missense variant Q1250H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for Q1250H, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.759478	Disordered	0.360484	Uncertain	0.881	0.554	0.750											-4.832	Likely Benign	0.252	Likely Benign	Likely Benign										0.117	Likely Benign	-1.91	Neutral	0.998	Probably Damaging	0.996	Probably Damaging	2.64	Benign	0.02	Affected			0.1084	0.2139		3	0	0.3	9.01
c.3753G>C	Q1251H 2D AIThe SynGAP1 missense variant Q1251H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a predominance of pathogenic calls: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all predict deleterious effects, while REVEL predicts a benign outcome. Two tools return uncertain results: ESM1b and AlphaMissense‑Optimized. High‑accuracy assessments further support a harmful interpretation: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic, and AlphaMissense‑Optimized remains inconclusive. No Foldetta stability data are available. Overall, the balance of evidence points to a pathogenic effect for Q1251H, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.771762	Disordered	0.363872	Uncertain	0.869	0.551	0.875											-7.561	In-Between	0.937	Likely Pathogenic	Ambiguous										0.176	Likely Benign	-3.71	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	2.44	Pathogenic	0.00	Affected			0.1132	0.2399		3	0	0.3	9.01
c.3753G>T	Q1251H 2D AIThe SynGAP1 missense variant Q1251H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a predominance of pathogenic calls: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all predict deleterious effects, while REVEL predicts a benign outcome. Two tools return uncertain results: ESM1b and AlphaMissense‑Optimized. High‑accuracy assessments further support a harmful interpretation: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic, and AlphaMissense‑Optimized remains inconclusive. No Foldetta stability data are available. Overall, the balance of evidence points to a pathogenic effect for Q1251H, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.771762	Disordered	0.363872	Uncertain	0.869	0.551	0.875											-7.561	In-Between	0.937	Likely Pathogenic	Ambiguous										0.176	Likely Benign	-3.71	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	2.44	Pathogenic	0.00	Affected			0.1132	0.2399		3	0	0.3	9.01
c.3756G>C	Q1252H 2D AIThe SynGAP1 missense variant Q1252H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as deleterious. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.759478	Disordered	0.371411	Uncertain	0.850	0.544	0.875											-6.891	Likely Benign	0.951	Likely Pathogenic	Ambiguous										0.175	Likely Benign	-4.02	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.95	Pathogenic	0.00	Affected			0.1038	0.2149		3	0	0.3	9.01
c.3756G>T	Q1252H 2D AIThe SynGAP1 missense variant Q1252H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain, SGM‑Consensus is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the preponderance of evidence from multiple in‑silico predictors indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.759478	Disordered	0.371411	Uncertain	0.850	0.544	0.875											-6.891	Likely Benign	0.951	Likely Pathogenic	Ambiguous										0.175	Likely Benign	-4.02	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.95	Pathogenic	0.00	Affected			0.1038	0.2149		3	0	0.3	9.01
c.3760G>C	E1254Q 2D AIThe SynGAP1 missense variant E1254Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessment shows AlphaMissense‑Optimized predicts benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—favors pathogenic (2 pathogenic vs. 1 benign). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy tools points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.657645	Disordered	0.403242	Uncertain	0.886	0.555	0.625											-9.041	Likely Pathogenic	0.511	Ambiguous	Likely Benign										0.207	Likely Benign	-2.18	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.35	Pathogenic	0.03	Affected			0.0768	0.5258		2	2	0.0	-0.98
c.3761A>G	E1254G 2D AIThe SynGAP1 missense variant E1254G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized indicates a benign change, but the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and the SGM Consensus suggests that the variant is most likely pathogenic, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.657645	Disordered	0.403242	Uncertain	0.886	0.555	0.625											-10.156	Likely Pathogenic	0.706	Likely Pathogenic	Likely Benign										0.315	Likely Benign	-4.52	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.34	Pathogenic	0.01	Affected			0.2636	0.5072		0	-2	3.1	-72.06
c.3774G>C	Q1258H 2D AIThe SynGAP1 missense variant Q1258H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also leans pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.486429	Structured	0.525814	Binding	0.859	0.577	0.250											-5.465	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.172	Likely Benign	-3.99	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.95	Pathogenic	0.00	Affected			0.0735	0.3066		3	0	0.3	9.01
c.3774G>T	Q1258H 2D AIThe SynGAP1 missense variant Q1258H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) is likely pathogenic; Foldetta results are unavailable. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.486429	Structured	0.525814	Binding	0.859	0.577	0.250											-5.465	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.172	Likely Benign	-3.99	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.95	Pathogenic	0.00	Affected			0.0735	0.3066		3	0	0.3	9.01
c.3775A>T	I1259F 2D AIThe SynGAP1 missense variant I1259F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and FATHMM, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are less decisive: AlphaMissense‑Optimized returns an uncertain result, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta data are unavailable. Overall, the majority of evidence (five pathogenic vs. three benign) points toward a pathogenic effect. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.494003	Structured	0.576405	Binding	0.885	0.574	0.250											-10.666	Likely Pathogenic	0.955	Likely Pathogenic	Ambiguous										0.301	Likely Benign	-1.68	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.55	Benign	0.03	Affected			0.0428	0.2563		1	0	-1.7	34.02
c.3776T>G	I1259S 2D AIThe SynGAP1 missense variant I1259S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled “Likely Pathogenic.” No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.494003	Structured	0.576405	Binding	0.885	0.574	0.250											-12.269	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.426	Likely Benign	-2.76	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.53	Benign	0.01	Affected			0.3004	0.1110		-1	-2	-5.3	-26.08
c.3784A>T	I1262F 2D AIThe SynGAP1 missense variant I1262F is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess functional impact uniformly indicate a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool in the dataset predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports that the variant is most likely pathogenic, and this conclusion is consistent with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.707863	Binding	0.886	0.576	0.125											-11.343	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.515	Likely Pathogenic	-3.32	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.81	Pathogenic	0.00	Affected			0.0532	0.2731		1	0	-1.7	34.02
c.3785T>G	I1262S 2D AIThe SynGAP1 missense variant I1262S is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion is not contradicted by ClinVar status, which currently has no entry for I1262S. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.707863	Binding	0.886	0.576	0.125											-15.167	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.483	Likely Benign	-4.98	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.80	Pathogenic	0.00	Affected			0.2943	0.1110		-1	-2	-5.3	-26.08
c.3820C>T	R1274C 2D AIThe SynGAP1 missense variant R1274C is listed in ClinVar with an “Uncertain” significance and is present in gnomAD (ID 6‑33447868‑C‑T). Prediction tools that agree on benign impact include REVEL, ESM1b, and AlphaMissense‑Optimized, while those that predict pathogenicity are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). AlphaMissense‑Default remains uncertain, and Foldetta results are unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus as pathogenic, and no Foldetta data to weigh in. Overall, the majority of evaluated tools (seven pathogenic vs. three benign) suggest a pathogenic effect. This consensus does not contradict the ClinVar “Uncertain” status, which remains inconclusive. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.613573	Disordered	0.779985	Binding	0.746	0.688	0.625					Uncertain		1	6-33447868-C-T			-6.467	Likely Benign	0.439	Ambiguous	Likely Benign										0.170	Likely Benign	-5.22	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.46	Pathogenic	0.00	Affected	3.77	5	0.3232	0.1517		-4	-3	7.0	-53.05
c.3863A>T	K1288M 2D AIThe SynGAP1 missense variant K1288M is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus indicates a likely pathogenic outcome; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of computational predictions (seven pathogenic vs. three benign) point to a pathogenic impact for K1288M. This conclusion is not contradicted by ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.827927	Disordered	0.814714	Binding	0.538	0.784	0.625											-3.355	Likely Benign	0.660	Likely Pathogenic	Likely Benign										0.246	Likely Benign	-4.89	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.06	Pathogenic	0.00	Affected			0.0985	0.3140		0	-1	5.8	3.02
c.443C>G	P148R 2D AIThe SynGAP1 missense variant P148R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from multiple in silico predictors and high‑accuracy tools suggests that P148R is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.500109	Binding	0.372	0.837	0.625											-12.079	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic										0.174	Likely Benign	-3.17	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.92	Benign	0.01	Affected			0.1615	0.3100		0	-2	-2.9	59.07
c.443C>T	P148L 2D AIThe SynGAP1 missense variant P148L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) indicate a pathogenic impact. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta results are unavailable. Overall, the consensus of the majority of tools points to a pathogenic effect. Because there is no ClinVar classification to contradict this, the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.500109	Binding	0.372	0.837	0.625											-10.375	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous										0.185	Likely Benign	-3.29	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.93	Benign	0.01	Affected			0.2229	0.5714		-3	-3	5.4	16.04
c.623C>A	P208Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P208Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and FATHMM. The majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and Foldetta. Two tools give uncertain results (AlphaMissense‑Optimized and Rosetta) and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as Pathogenic, reinforcing a deleterious prediction. Overall, the evidence strongly favors a pathogenic classification, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.271506	Structured	0.399506	Uncertain	0.864	0.345	0.125											-9.746	Likely Pathogenic	0.906	Likely Pathogenic	Ambiguous	3.30	Destabilizing	0.7	0.75	Ambiguous	2.03	Destabilizing	1.23	Destabilizing	0.411	Likely Benign	-6.78	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.78	Benign	0.00	Affected			0.1570	0.4663		0	-1	-1.9	31.01
c.623C>G	P208R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P208R missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and FATHMM. The majority of other in silico predictors (FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) and the SGM‑Consensus score (Likely Pathogenic) all indicate a pathogenic impact, while Rosetta remains uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the preponderance of pathogenic predictions and the absence of any benign consensus, the variant is most likely pathogenic, with no contradiction to ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.271506	Structured	0.399506	Uncertain	0.864	0.345	0.125											-11.929	Likely Pathogenic	0.966	Likely Pathogenic	Likely Pathogenic	5.25	Destabilizing	1.6	1.39	Ambiguous	3.32	Destabilizing	1.16	Destabilizing	0.472	Likely Benign	-7.50	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.75	Benign	0.00	Affected			0.1676	0.3118		0	-2	-2.9	59.07
c.623C>T	P208L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P208L has no ClinVar entry and is present in gnomAD (ID 6‑33435265‑C‑T). Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, while those that agree on a pathogenic effect include FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Predictions that are inconclusive are Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus as likely pathogenic, and Foldetta as uncertain. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.271506	Structured	0.399506	Uncertain	0.864	0.345	0.125								6-33435265-C-T	1	6.20e-7	-10.013	Likely Pathogenic	0.889	Likely Pathogenic	Ambiguous	2.35	Destabilizing	0.5	0.04	Likely Benign	1.20	Ambiguous	0.67	Ambiguous	0.466	Likely Benign	-8.49	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.75	Benign	0.01	Affected	3.44	12	0.2219	0.6191		-3	-3	5.4	16.04
c.764A>T	D255V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D255V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from premPS and FATHMM, while pathogenic predictions are made by SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results are reported by FoldX, Rosetta, and Foldetta. High‑accuracy methods reinforce the pathogenic interpretation: AlphaMissense‑Optimized predicts Pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, remains Uncertain. Overall, the consensus of available predictions points to a pathogenic effect for D255V, and this conclusion is consistent with the lack of ClinVar annotation (no contradiction). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.501700	Disordered	0.219132	Uncertain	0.801	0.273	0.250											-13.575	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.76	Ambiguous	0.2	1.07	Ambiguous	1.42	Ambiguous	0.16	Likely Benign	0.895	Likely Pathogenic	-7.77	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	5.75	Benign	0.00	Affected			0.0684	0.5162		-2	-3	7.7	-15.96
c.766A>T	N256Y 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N256Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that classify the variant as benign include FoldX, Foldetta, premPS, and FATHMM, whereas the majority of tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—label it pathogenic. The high‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the preponderance of evidence from standard predictors and the two high‑accuracy pathogenic calls suggests that the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.414856	Structured	0.234105	Uncertain	0.826	0.271	0.250											-10.881	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.17	Likely Benign	0.2	-0.80	Ambiguous	-0.32	Likely Benign	0.30	Likely Benign	0.868	Likely Pathogenic	-6.85	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	5.83	Benign	0.00	Affected			0.0493	0.5881		-2	-2	2.2	49.07
c.782A>T	D261V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D261V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include premPS, SIFT, and FATHMM, while those that predict a pathogenic effect comprise SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of available predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.284882	Structured	0.422514	Uncertain	0.883	0.264	0.125											-12.138	Likely Pathogenic	0.923	Likely Pathogenic	Ambiguous	1.72	Ambiguous	0.6	-0.68	Ambiguous	0.52	Ambiguous	-0.01	Likely Benign	0.869	Likely Pathogenic	-5.50	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	5.73	Benign	0.08	Tolerated			0.0553	0.4734		-2	-3	7.7	-15.96
c.784A>T	N262Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N262Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include premPS, FATHMM, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. The remaining tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Default) are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of predictions (seven pathogenic vs. three benign) lean toward a pathogenic impact, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.284882	Structured	0.399879	Uncertain	0.912	0.240	0.000											-12.177	Likely Pathogenic	0.490	Ambiguous	Likely Benign	1.86	Ambiguous	0.5	0.52	Ambiguous	1.19	Ambiguous	0.36	Likely Benign	0.858	Likely Pathogenic	-6.48	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	5.85	Benign	0.01	Affected			0.0445	0.3877		-2	-2	2.2	49.07
c.799T>G	W267G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W267G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify it as pathogenic: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy methods corroborate this: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Thus, the variant is most likely pathogenic, with no contradiction to its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.216401	Structured	0.298060	Uncertain	0.943	0.274	0.000											-15.020	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	4.40	Destabilizing	0.2	3.99	Destabilizing	4.20	Destabilizing	1.20	Destabilizing	0.678	Likely Pathogenic	-11.95	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.96	Pathogenic	0.03	Affected			0.4049	0.1481		-7	-2	0.5	-129.16
c.800G>T	W267L 2D AIThe SynGAP1 missense variant W267L is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. No tool in the dataset predicts a benign effect. Uncertain or inconclusive results come from FoldX, Rosetta, Foldetta, and premPS, which are treated as unavailable evidence. High‑accuracy assessments further support a damaging effect: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic,” while Foldetta’s stability prediction is uncertain. Overall, the evidence strongly indicates that W267L is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.216401	Structured	0.298060	Uncertain	0.943	0.274	0.000											-13.670	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	1.19	Ambiguous	0.7	1.31	Ambiguous	1.25	Ambiguous	0.75	Ambiguous	0.628	Likely Pathogenic	-11.95	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.93	Pathogenic	0.01	Affected			0.2122	0.2843		-2	-2	4.7	-73.05
c.802A>T	I268F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I268F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity uniformly indicate a deleterious effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while the SGM‑Consensus score is “Likely Pathogenic.” No tool in the dataset predicts a benign outcome; only Rosetta and Foldetta are uncertain. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) remains uncertain. Overall, the consensus of available predictions strongly supports a pathogenic classification for I268F, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.216401	Structured	0.314336	Uncertain	0.951	0.264	0.000											-11.426	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	2.85	Destabilizing	0.7	0.59	Ambiguous	1.72	Ambiguous	1.00	Destabilizing	0.685	Likely Pathogenic	-3.68	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.53	Pathogenic	0.00	Affected			0.0427	0.2158		1	0	-1.7	34.02
c.803T>G	I268S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I268S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity all agree that the variant is deleterious: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic. No tool predicts a benign effect. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, indicates a destabilizing, pathogenic effect. All available predictions are concordant and supportive. Based on these computational assessments, the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.216401	Structured	0.314336	Uncertain	0.951	0.264	0.000											-13.032	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	4.93	Destabilizing	0.1	4.54	Destabilizing	4.74	Destabilizing	2.10	Destabilizing	0.841	Likely Pathogenic	-5.34	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.53	Pathogenic	0.00	Affected			0.2037	0.0530		-1	-2	-5.3	-26.08
c.808G>C	E270Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E270Q missense variant is not reported in ClinVar (status: None) and has no entry in gnomAD. Prediction tools that indicate a benign effect include REVEL, FoldX, and premPS, whereas the majority of tools predict pathogenicity: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates several high‑accuracy predictors, classifies the variant as Likely Pathogenic. High‑accuracy methods give the following results: AlphaMissense‑Optimized is Uncertain; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is Uncertain. Rosetta alone is Uncertain, and Foldetta’s uncertainty reflects limited stability change evidence. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion does not contradict ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.144935	Structured	0.382573	Uncertain	0.938	0.231	0.125											-11.096	Likely Pathogenic	0.886	Likely Pathogenic	Ambiguous	0.00	Likely Benign	0.2	1.00	Ambiguous	0.50	Ambiguous	0.46	Likely Benign	0.418	Likely Benign	-2.76	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.65	Pathogenic	0.03	Affected			0.1044	0.4015		2	2	0.0	-0.98
c.809A>G	E270G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E270G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled Likely Pathogenic. Rosetta also predicts pathogenicity, while FoldX, Foldetta, and premPS are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. No tool predicts a benign effect. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.144935	Structured	0.382573	Uncertain	0.938	0.231	0.125											-13.759	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	1.23	Ambiguous	0.2	2.37	Destabilizing	1.80	Ambiguous	0.61	Ambiguous	0.576	Likely Pathogenic	-6.43	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.63	Pathogenic	0.00	Affected			0.3254	0.3876		0	-2	3.1	-72.06
c.811G>T	A271S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A271S is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Predictions that are inconclusive are Foldetta and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic impact for A271S, which contrasts with the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.125101	Structured	0.413873	Uncertain	0.939	0.220	0.125					Uncertain		1				-9.552	Likely Pathogenic	0.629	Likely Pathogenic	Likely Benign	0.19	Likely Benign	0.1	1.47	Ambiguous	0.83	Ambiguous	1.14	Destabilizing	0.453	Likely Benign	-2.76	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	0.64	Pathogenic	0.03	Affected			0.2260	0.3312		1	1	-2.6	16.00
c.812C>G	A271G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A271G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. FoldX, Rosetta, and Foldetta provide uncertain or unavailable stability results and are not considered evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic, and Foldetta as unavailable. Overall, the balance of evidence (seven pathogenic versus three benign predictions) indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.125101	Structured	0.413873	Uncertain	0.939	0.220	0.125											-9.508	Likely Pathogenic	0.183	Likely Benign	Likely Benign	1.73	Ambiguous	0.1	1.43	Ambiguous	1.58	Ambiguous	1.31	Destabilizing	0.434	Likely Benign	-3.68	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	0.89	Pathogenic	0.01	Affected			0.1869	0.2388		1	0	-2.2	-14.03
c.812C>T	A271V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A271V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, premPS, and Foldetta, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: AlphaMissense‑Optimized and Rosetta. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized remains inconclusive; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.125101	Structured	0.413873	Uncertain	0.939	0.220	0.125											-8.185	Likely Pathogenic	0.940	Likely Pathogenic	Ambiguous	-0.22	Likely Benign	0.2	0.78	Ambiguous	0.28	Likely Benign	0.37	Likely Benign	0.466	Likely Benign	-3.68	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	0.69	Pathogenic	0.02	Affected			0.0986	0.4409		0	0	2.4	28.05
c.844T>G	C282G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C282G is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms predict a pathogenic impact: FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). The high‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; SGM‑Consensus is pathogenic; Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the overwhelming agreement among pathogenic predictors and the high‑accuracy tools, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.348535	Uncertain	0.942	0.250	0.000											-15.830	Likely Pathogenic	0.837	Likely Pathogenic	Ambiguous	2.60	Destabilizing	0.1	2.83	Destabilizing	2.72	Destabilizing	1.60	Destabilizing	0.482	Likely Benign	-11.03	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.64	Pathogenic	0.04	Affected			0.3229	0.2238		-3	-3	-2.9	-46.09
c.847G>C	E283Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E283Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, and Foldetta. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). The premPS score is uncertain and does not contribute to the consensus. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of tools (nine pathogenic vs. four benign) predict a pathogenic impact. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.358602	Uncertain	0.950	0.249	0.000											-10.650	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.48	Likely Benign	0.1	-0.01	Likely Benign	0.24	Likely Benign	0.61	Ambiguous	0.372	Likely Benign	-2.76	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.67	Pathogenic	0.01	Affected			0.1432	0.5389		2	2	0.0	-0.98
c.848A>G	E283G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E283G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while the single uncertain call from premPS is treated as unavailable. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the unanimous pathogenic predictions and the absence of any benign calls, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.358602	Uncertain	0.950	0.249	0.000											-13.937	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.13	Destabilizing	0.1	2.74	Destabilizing	2.94	Destabilizing	0.55	Ambiguous	0.559	Likely Pathogenic	-6.43	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.63	Pathogenic	0.01	Affected			0.3123	0.4842		0	-2	3.1	-72.06
c.853T>G	C285G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C285G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a pathogenic interpretation: SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict deleterious effects. Tools that assess protein stability (FoldX, Rosetta, Foldetta) and AlphaMissense‑Optimized return uncertain results, providing no clear evidence for or against pathogenicity. High‑accuracy assessments further support a likely pathogenic verdict: the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled Likely Pathogenic, while AlphaMissense‑Optimized and Foldetta remain inconclusive. Overall, the consensus of the majority of predictors indicates that the variant is most likely pathogenic, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.144935	Structured	0.375400	Uncertain	0.946	0.250	0.000											-9.937	Likely Pathogenic	0.859	Likely Pathogenic	Ambiguous	1.26	Ambiguous	0.0	1.57	Ambiguous	1.42	Ambiguous	1.50	Destabilizing	0.564	Likely Pathogenic	-9.86	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.78	Pathogenic	0.04	Affected			0.3509	0.2922		-3	-3	-2.9	-46.09
c.874G>T	A292S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A292S is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and FoldX, whereas a majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), PolyPhen‑2 HumDiv, PolyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and PROVEAN. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as uncertain. No prediction or folding‑stability result is missing; uncertain outcomes are treated as unavailable. Overall, the balance of evidence favors a pathogenic classification. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.247041	Structured	0.362042	Uncertain	0.929	0.256	0.000											-8.514	Likely Pathogenic	0.804	Likely Pathogenic	Ambiguous	0.40	Likely Benign	0.2	2.13	Destabilizing	1.27	Ambiguous	0.70	Ambiguous	0.364	Likely Benign	-2.76	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.69	Pathogenic	0.03	Affected			0.2850	0.6389		1	1	-2.6	16.00
c.875C>G	A292G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A292G is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, SIFT, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus from AlphaMissense‑Optimized is benign, whereas the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain, and individual FoldX and Rosetta predictions are also inconclusive. Overall, the majority of evidence points to a pathogenic impact, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.247041	Structured	0.362042	Uncertain	0.929	0.256	0.000											-9.692	Likely Pathogenic	0.713	Likely Pathogenic	Likely Benign	0.88	Ambiguous	0.1	1.83	Ambiguous	1.36	Ambiguous	1.05	Destabilizing	0.323	Likely Benign	-3.68	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.74	Pathogenic	0.10	Tolerated			0.2187	0.5054		1	0	-2.2	-14.03
c.875C>T	A292V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A292V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact; premPS is uncertain and therefore not counted. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the overwhelming agreement among these predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.247041	Structured	0.362042	Uncertain	0.929	0.256	0.000											-11.170	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	2.04	Destabilizing	0.5	4.60	Destabilizing	3.32	Destabilizing	0.85	Ambiguous	0.430	Likely Benign	-3.68	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.75	Pathogenic	0.03	Affected			0.1272	0.6253		0	0	2.4	28.05
c.886T>C	S296P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S296P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, FoldX, Rosetta, and SIFT, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. When predictions are grouped by agreement, four tools predict benign and seven predict pathogenic, with premPS remaining uncertain. High‑accuracy methods give a mixed signal: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus, derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, reports a benign effect. Thus, the majority of evidence leans toward pathogenicity, and this conclusion is consistent with the lack of ClinVar annotation and gnomAD absence, which do not contradict the prediction. Overall, the variant is most likely pathogenic based on the current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.444081	Structured	0.282669	Uncertain	0.887	0.284	0.250											-8.302	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.04	Likely Benign	0.4	0.18	Likely Benign	0.11	Likely Benign	0.72	Ambiguous	0.439	Likely Benign	-3.74	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.92	Pathogenic	0.12	Tolerated			0.2273	0.6320		1	-1	-0.8	10.04
c.916G>C	V306L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V306L missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are FoldX, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Uncertain results come from Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely benign, and Foldetta is inconclusive. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.363090	Structured	0.315026	Uncertain	0.896	0.287	0.125											-3.633	Likely Benign	0.267	Likely Benign	Likely Benign	2.14	Destabilizing	0.2	1.47	Ambiguous	1.81	Ambiguous	0.75	Ambiguous	0.161	Likely Benign	-1.01	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	1.76	Pathogenic	0.21	Tolerated			0.0823	0.4117		2	1	-0.4	14.03
c.920T>C	F307S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F307S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. In silico predictors that provide a definitive call all classify the variant as pathogenic: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic verdict. Predictions that are inconclusive or uncertain include FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) remains uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.298791	Structured	0.327302	Uncertain	0.900	0.315	0.125											-12.282	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.58	Ambiguous	0.2	1.22	Ambiguous	1.40	Ambiguous	0.99	Ambiguous	0.766	Likely Pathogenic	-7.32	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.97	Pathogenic	0.01	Affected			0.4576	0.0758		-3	-2	-3.6	-60.10
c.922T>G	W308G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W308G is not reported in ClinVar (ClinVar status: not reported) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity all converge on a deleterious effect: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic outcome. No tool predicts a benign effect, so the benign group is empty. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the unanimous predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which simply lacks an entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.333942	Uncertain	0.907	0.314	0.125											-16.271	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	6.88	Destabilizing	0.2	5.07	Destabilizing	5.98	Destabilizing	1.97	Destabilizing	0.860	Likely Pathogenic	-11.95	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	0.48	Pathogenic	0.00	Affected			0.4884	0.1644		-7	-2	0.5	-129.16
c.923G>T	W308L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W308L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates “Likely Pathogenic.” Only Rosetta and premPS yield uncertain results, which are treated as unavailable evidence. High‑accuracy assessments reinforce the pathogenic prediction: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No tools predict benign effects. **Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available).** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.333942	Uncertain	0.907	0.314	0.125											-13.349	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	3.53	Destabilizing	0.5	1.52	Ambiguous	2.53	Destabilizing	0.53	Ambiguous	0.811	Likely Pathogenic	-11.95	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	0.49	Pathogenic	0.00	Affected			0.2731	0.2754		-2	-2	4.7	-73.05
c.929A>G	E310G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E310G is listed in ClinVar as Pathogenic (ClinVar ID 2732842.0) and is not reported in gnomAD. Prediction tools that assess the variant’s effect largely agree on a deleterious outcome: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while only premPS predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenicity. Consequently, the variant is most likely pathogenic, and this prediction is consistent with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.222385	Structured	0.346136	Uncertain	0.914	0.337	0.125					Pathogenic		1				-14.132	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	2.38	Destabilizing	0.7	3.56	Destabilizing	2.97	Destabilizing	0.36	Likely Benign	0.848	Likely Pathogenic	-6.43	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.12	Pathogenic	0.00	Affected	3.38	19	0.2736	0.6932		-2	0	3.1	-72.06
c.932A>T	H311L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H311L missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include AlphaMissense‑Optimized, Foldetta, premPS, and Rosetta. Tools that predict a pathogenic outcome are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default; FoldX is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labeling it likely pathogenic, and Foldetta predicting a benign effect. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.229226	Structured	0.354792	Uncertain	0.902	0.314	0.125											-10.119	Likely Pathogenic	0.575	Likely Pathogenic	Likely Benign	-0.53	Ambiguous	0.0	-0.04	Likely Benign	-0.29	Likely Benign	0.43	Likely Benign	0.663	Likely Pathogenic	-7.99	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.87	Pathogenic	0.02	Affected			0.0961	0.5292		-2	-3	7.0	-23.98
c.933C>A	H311Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H311Q missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, FoldX, Rosetta, and Foldetta. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: AlphaMissense‑Optimized and premPS. The high‑accuracy consensus methods give mixed signals: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, more tools (seven) predict pathogenicity than benign (four), and the SGM Consensus supports a pathogenic classification, while Foldetta offers a contrary benign prediction. The variant is most likely pathogenic based on the aggregate predictions, and this assessment does not contradict the absence of a ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.229226	Structured	0.354792	Uncertain	0.902	0.314	0.125											-8.656	Likely Pathogenic	0.792	Likely Pathogenic	Ambiguous	0.15	Likely Benign	0.1	0.39	Likely Benign	0.27	Likely Benign	0.92	Ambiguous	0.414	Likely Benign	-5.95	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.94	Pathogenic	0.03	Affected			0.1490	0.3775		3	0	-0.3	-9.01
c.933C>G	H311Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H311Q missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, and Foldetta. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. With seven pathogenic versus four benign predictions, the overall consensus leans toward pathogenicity. This conclusion does not contradict ClinVar status, as no ClinVar classification is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.229226	Structured	0.354792	Uncertain	0.902	0.314	0.125											-8.656	Likely Pathogenic	0.792	Likely Pathogenic	Ambiguous	0.15	Likely Benign	0.1	0.39	Likely Benign	0.27	Likely Benign	0.92	Ambiguous	0.414	Likely Benign	-5.95	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.94	Pathogenic	0.03	Affected			0.1490	0.3775		3	0	-0.3	-9.01
c.935T>C	F312S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F312S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). All available in‑silico predictors classify the variant as pathogenic: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts pathogenic. Based on the unanimous pathogenic predictions and the absence of any benign calls, the variant is most likely pathogenic, with no contradiction to ClinVar status (which is currently unreported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.225814	Structured	0.361163	Uncertain	0.915	0.317	0.000											-14.075	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	3.74	Destabilizing	0.3	5.64	Destabilizing	4.69	Destabilizing	2.70	Destabilizing	0.880	Likely Pathogenic	-7.35	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.17	Pathogenic	0.00	Affected			0.3563	0.1578		-3	-2	-3.6	-60.10
c.938A>G	E313G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E313G is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—all of which classify the variant as pathogenic. No tool predicts a benign outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is Pathogenic. Taken together, the overwhelming consensus from both general and high‑accuracy predictors indicates that E313G is most likely pathogenic, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.170161	Structured	0.366526	Uncertain	0.898	0.304	0.125											-14.615	Likely Pathogenic	0.912	Likely Pathogenic	Ambiguous	2.00	Destabilizing	0.5	2.42	Destabilizing	2.21	Destabilizing	0.79	Ambiguous	0.750	Likely Pathogenic	-5.50	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.83	Pathogenic	0.01	Affected			0.2638	0.6680		0	-2	3.1	-72.06
c.941T>C	F314S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F314S (located in the C2 domain) is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify it as pathogenic: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a destabilizing, pathogenic effect. Thus, the variant is most likely pathogenic based on predictions, and this assessment does not contradict the ClinVar status, which simply lacks an entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.173081	Structured	0.374049	Uncertain	0.900	0.271	0.125											-14.371	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	4.51	Destabilizing	0.4	3.36	Destabilizing	3.94	Destabilizing	2.59	Destabilizing	0.735	Likely Pathogenic	-6.95	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.15	Pathogenic	0.00	Affected			0.4113	0.0600		-3	-2	-3.6	-60.10
c.945C>A	N315K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N315K is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and Foldetta. Tools that agree on a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: AlphaMissense‑Optimized and premPS. High‑accuracy assessments show that the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. No other high‑accuracy tool provides a conclusive result. Overall, the majority of predictions (seven pathogenic vs. five benign, with two uncertain) indicate that the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.118441	Structured	0.379740	Uncertain	0.862	0.253	0.125											-10.380	Likely Pathogenic	0.872	Likely Pathogenic	Ambiguous	-0.03	Likely Benign	0.1	0.08	Likely Benign	0.03	Likely Benign	0.87	Ambiguous	0.340	Likely Benign	-3.27	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.98	Pathogenic	0.54	Tolerated			0.2268	0.6436		1	0	-0.4	14.07
c.945C>G	N315K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N315K is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and Foldetta. Tools that agree on a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: AlphaMissense‑Optimized and premPS. High‑accuracy assessments show that AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the majority of evidence (seven pathogenic vs. five benign, with two uncertain) points to a pathogenic impact. Thus, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.118441	Structured	0.379740	Uncertain	0.862	0.253	0.125											-10.380	Likely Pathogenic	0.872	Likely Pathogenic	Ambiguous	-0.03	Likely Benign	0.1	0.08	Likely Benign	0.03	Likely Benign	0.87	Ambiguous	0.340	Likely Benign	-3.27	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.98	Pathogenic	0.54	Tolerated			0.2268	0.6436		1	0	-0.4	14.07
c.948C>A	N316K 2D AIThe SynGAP1 missense variant N316K is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include REVEL and SIFT, whereas the majority of tools predict a pathogenic outcome: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as uncertain. No other high‑confidence predictions are available. Overall, the preponderance of evidence points to a pathogenic effect for N316K, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.118441	Structured	0.385187	Uncertain	0.817	0.246	0.125											-10.711	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic	0.52	Ambiguous	0.7	0.86	Ambiguous	0.69	Ambiguous	0.67	Ambiguous	0.254	Likely Benign	-3.87	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.77	Pathogenic	0.13	Tolerated			0.2220	0.6593		1	0	-0.4	14.07
c.948C>G	N316K 2D AISynGAP1 missense variant N316K is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and SIFT, whereas a majority of tools predict pathogenicity: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, yields an uncertain result and is treated as unavailable evidence. Overall, the preponderance of computational predictions indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.118441	Structured	0.385187	Uncertain	0.817	0.246	0.125											-10.711	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic	0.52	Ambiguous	0.7	0.86	Ambiguous	0.69	Ambiguous	0.67	Ambiguous	0.254	Likely Benign	-3.87	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.77	Pathogenic	0.13	Tolerated			0.2220	0.6593		1	0	-0.4	14.07
c.977A>T	H326L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H326L missense variant is not reported in ClinVar (status: None) and has no entry in gnomAD. Prediction tools that agree on a benign effect include SIFT, premPS, Rosetta, and Foldetta. Tools that agree on a pathogenic effect include REVEL, SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy methods give mixed results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts likely pathogenic; and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) predicts benign. No evidence is available from FoldX or AlphaMissense‑Optimized to support either outcome. Overall, the majority of predictions (nine pathogenic vs. four benign) indicate that H326L is most likely pathogenic, and this assessment does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.342579	Structured	0.418150	Uncertain	0.944	0.455	0.000											-10.421	Likely Pathogenic	0.888	Likely Pathogenic	Ambiguous	-0.85	Ambiguous	0.2	0.36	Likely Benign	-0.25	Likely Benign	0.44	Likely Benign	0.627	Likely Pathogenic	-9.64	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.95	Pathogenic	0.08	Tolerated			0.0992	0.5799		-2	-3	7.0	-23.98
c.978T>A	H326Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H326Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, and SIFT, whereas a majority of tools predict a pathogenic outcome: premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Two tools, Foldetta (combining FoldX‑MD and Rosetta) and Rosetta alone, return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for H326Q. This conclusion is not contradicted by ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.342579	Structured	0.418150	Uncertain	0.944	0.455	0.000											-8.688	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.46	Likely Benign	0.1	1.67	Ambiguous	1.07	Ambiguous	1.00	Destabilizing	0.444	Likely Benign	-6.89	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.07	Pathogenic	0.10	Tolerated			0.1485	0.3500		3	0	-0.3	-9.01
c.978T>G	H326Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H326Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, and SIFT, whereas a majority of tools predict a pathogenic outcome: premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Two tools, Foldetta (combining FoldX‑MD and Rosetta) and Rosetta alone, return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus also indicates likely pathogenic, while Foldetta remains uncertain. Overall, the preponderance of evidence from multiple independent predictors points to a pathogenic effect for H326Q. This conclusion is not contradicted by ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.342579	Structured	0.418150	Uncertain	0.944	0.455	0.000											-8.688	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.46	Likely Benign	0.1	1.67	Ambiguous	1.07	Ambiguous	1.00	Destabilizing	0.444	Likely Benign	-6.89	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.07	Pathogenic	0.10	Tolerated			0.1485	0.3500		3	0	-0.3	-9.01
c.1003C>A	R335S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R335S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL, premPS, and SIFT; pathogenic predictions from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. No evidence from FoldX or Rosetta alone is available. Based on the preponderance of pathogenic predictions and the high‑accuracy tools, the variant is most likely pathogenic, which is consistent with the absence of ClinVar reporting and gnomAD data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.305330	Structured	0.331028	Uncertain	0.483	0.428	0.500											-9.286	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	0.68	Ambiguous	0.1	0.72	Ambiguous	0.70	Ambiguous	0.14	Likely Benign	0.184	Likely Benign	-3.30	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.89	Pathogenic	0.11	Tolerated			0.2598	0.4005		0	-1	3.7	-69.11
c.1003C>G	R335G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R335G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, and SIFT, whereas those that agree on a pathogenic effect include SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, more tools predict pathogenicity than benignity, and the high‑accuracy consensus also leans pathogenic. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.305330	Structured	0.331028	Uncertain	0.483	0.428	0.500											-11.860	Likely Pathogenic	0.880	Likely Pathogenic	Ambiguous	1.01	Ambiguous	0.1	0.44	Likely Benign	0.73	Ambiguous	0.20	Likely Benign	0.194	Likely Benign	-4.77	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.01	Pathogenic	0.10	Tolerated			0.3000	0.3554		-3	-2	4.1	-99.14
c.1004G>T	R335L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R335L is not listed in ClinVar (ClinVar ID None) and has no reported allele in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, and premPS. Tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized and FoldX are uncertain and are treated as unavailable for pathogenicity inference. High‑accuracy assessments: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, predicts pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign. Overall, the majority of predictions (8 pathogenic vs. 4 benign) indicate that the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar assertion is present. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.305330	Structured	0.331028	Uncertain	0.483	0.428	0.500											-13.226	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	0.51	Ambiguous	0.0	-0.19	Likely Benign	0.16	Likely Benign	0.40	Likely Benign	0.196	Likely Benign	-4.77	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.73	Pathogenic	0.04	Affected			0.1382	0.4753		-3	-2	8.3	-43.03
c.1009A>C	K337Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K337Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, and Foldetta. Those that predict a pathogenic effect comprise SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: AlphaMissense‑Optimized and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as benign. Overall, the majority of predictions (8 pathogenic vs. 4 benign) indicate that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.348540	Uncertain	0.449	0.438	0.500											-9.944	Likely Pathogenic	0.934	Likely Pathogenic	Ambiguous	0.00	Likely Benign	0.0	0.88	Ambiguous	0.44	Likely Benign	0.43	Likely Benign	0.305	Likely Benign	-3.48	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.70	Pathogenic	0.01	Affected			0.3672	0.1219		1	1	0.4	-0.04
c.1010A>C	K337T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K337T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two consensus groups: benign predictions come from REVEL, FoldX, and premPS, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Three tools report uncertainty: Rosetta, Foldetta, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Pathogenic. In the high‑accuracy subset, AlphaMissense‑Optimized remains uncertain, SGM‑Consensus is Likely Pathogenic, and Foldetta is uncertain. Taken together, the majority of evidence points toward a deleterious effect. Therefore, K337T is most likely pathogenic, and this assessment does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.348540	Uncertain	0.449	0.438	0.500											-10.896	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous	0.45	Likely Benign	0.2	1.33	Ambiguous	0.89	Ambiguous	0.25	Likely Benign	0.338	Likely Benign	-5.32	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.70	Pathogenic	0.01	Affected			0.1741	0.3354		0	-1	3.2	-27.07
c.1011G>C	K337N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K337N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include REVEL, FoldX, Rosetta, premPS, and SIFT. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions (seven pathogenic vs. five benign) and the high‑accuracy consensus lean toward a pathogenic impact. Thus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.348540	Uncertain	0.449	0.438	0.500											-13.095	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	0.12	Likely Benign	0.1	0.36	Likely Benign	0.24	Likely Benign	-0.02	Likely Benign	0.280	Likely Benign	-4.38	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.87	Pathogenic	0.11	Tolerated			0.2945	0.1315		1	0	0.4	-14.07
c.1011G>T	K337N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K337N is not reported in ClinVar and has no entries in gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, Rosetta, premPS, and SIFT, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. With seven tools supporting pathogenicity versus five supporting benign, the overall prediction leans toward pathogenic. No ClinVar entry contradicts this assessment, and the variant is absent from gnomAD, so the pathogenic prediction is not challenged by population data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.348540	Uncertain	0.449	0.438	0.500											-13.095	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	0.12	Likely Benign	0.1	0.36	Likely Benign	0.24	Likely Benign	-0.02	Likely Benign	0.280	Likely Benign	-4.38	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.87	Pathogenic	0.11	Tolerated			0.2945	0.1315		1	0	0.4	-14.07
c.1046C>A	P349Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 P349Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and AlphaMissense‑Optimized, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. The remaining tools (FoldX, Rosetta, premPS, AlphaMissense‑Default, Foldetta) give uncertain or inconclusive results. High‑accuracy assessments further clarify the variant’s likely effect: AlphaMissense‑Optimized predicts a benign outcome; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, remains uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not conflict with the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.167087	Structured	0.348607	Uncertain	0.947	0.396	0.000											-10.545	Likely Pathogenic	0.508	Ambiguous	Likely Benign	0.98	Ambiguous	0.1	1.87	Ambiguous	1.43	Ambiguous	0.91	Ambiguous	0.345	Likely Benign	-6.40	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	1.54	Pathogenic	0.06	Tolerated			0.1480	0.4766		0	-1	-1.9	31.01
c.1046C>G	P349R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P349R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and Rosetta. Uncertain or inconclusive results come from FoldX, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for P349R. This conclusion is not contradicted by ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.167087	Structured	0.348607	Uncertain	0.947	0.396	0.000											-14.001	Likely Pathogenic	0.791	Likely Pathogenic	Ambiguous	0.99	Ambiguous	0.1	2.15	Destabilizing	1.57	Ambiguous	0.93	Ambiguous	0.335	Likely Benign	-7.22	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	1.55	Pathogenic	0.01	Affected			0.1395	0.3009		0	-2	-2.9	59.07
c.1046C>T	P349L 2D AIThe SynGAP1 missense variant P349L is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and AlphaMissense‑Optimized, whereas the majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy methods give conflicting results: AlphaMissense‑Optimized reports a benign outcome, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect, and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. Other stability‑based predictors (FoldX, Rosetta, premPS) are also inconclusive. Overall, the preponderance of evidence from the consensus of multiple in‑silico tools points to a pathogenic effect for P349L. This prediction does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.167087	Structured	0.348607	Uncertain	0.947	0.396	0.000											-11.734	Likely Pathogenic	0.650	Likely Pathogenic	Likely Benign	0.70	Ambiguous	0.6	1.17	Ambiguous	0.94	Ambiguous	0.57	Ambiguous	0.326	Likely Benign	-8.04	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	1.51	Pathogenic	0.00	Affected			0.2222	0.6867		-3	-3	5.4	16.04
c.1091C>G	P364R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P364R missense variant is not reported in ClinVar (status: None) and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain or inconclusive results come from FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments: AlphaMissense‑Optimized predicts benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic; Foldetta’s stability analysis is uncertain. Overall, the majority of evaluated tools (seven pathogenic vs. three benign) indicate that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.390993	Structured	0.439474	Uncertain	0.942	0.590	0.250											-12.652	Likely Pathogenic	0.715	Likely Pathogenic	Likely Benign	0.95	Ambiguous	0.7	0.88	Ambiguous	0.92	Ambiguous	0.73	Ambiguous	0.416	Likely Benign	-6.76	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	1.57	Pathogenic	0.12	Tolerated			0.1520	0.3977		0	-2	-2.9	59.07
c.1091C>T	P364L 2D 3DClick to see structure in 3D Viewer AISynGAP1 P364L is reported in gnomAD (ID 6‑33437996‑C‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, SIFT, AlphaMissense‑Optimized, and Foldetta; pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Three tools—FoldX, Rosetta, and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign. Overall, the balance of evidence slightly favors a benign effect, and this conclusion does not contradict any ClinVar classification because none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.390993	Structured	0.439474	Uncertain	0.942	0.590	0.250								6-33437996-C-T			-10.620	Likely Pathogenic	0.457	Ambiguous	Likely Benign	0.88	Ambiguous	0.9	-0.73	Ambiguous	0.08	Likely Benign	0.31	Likely Benign	0.387	Likely Benign	-7.78	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	1.54	Pathogenic	0.18	Tolerated	3.39	20	0.2200	0.6207		-3	-3	5.4	16.04
c.1207A>C	K403Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K403Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and FATHMM. In contrast, a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score. The premPS assessment is uncertain and does not influence the overall consensus. High‑accuracy analyses show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar claim exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.275179	Structured	0.424920	Uncertain	0.960	0.372	0.000											-12.479	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	0.36	Likely Benign	0.0	0.27	Likely Benign	0.32	Likely Benign	0.70	Ambiguous	0.376	Likely Benign	-3.59	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	3.76	Benign	0.01	Affected			0.4405	0.1954		1	1	0.4	-0.04
c.1244A>G	E415G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E415G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Stability‑based methods (FoldX, Rosetta, premPS) and Foldetta are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic impact for E415G. This prediction is consistent with the lack of ClinVar annotation and does not contradict any existing ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.100716	Structured	0.330366	Uncertain	0.915	0.236	0.000											-12.244	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	1.16	Ambiguous	0.2	0.88	Ambiguous	1.02	Ambiguous	0.65	Ambiguous	0.432	Likely Benign	-6.45	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.20	Benign	0.01	Affected			0.2518	0.3158		0	-2	3.1	-72.06
c.1256A>G	E419G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E419G is listed in ClinVar with an uncertain significance (ClinVar ID 2004834.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus confirms likely pathogenic, and the Foldetta stability analysis is inconclusive. No evidence from FoldX, Rosetta, or premPS is available. Overall, the preponderance of predictions indicates that E419G is most likely pathogenic, which contrasts with the current ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.371949	Uncertain	0.961	0.261	0.000					Uncertain		1				-10.589	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	1.41	Ambiguous	0.0	1.94	Ambiguous	1.68	Ambiguous	0.83	Ambiguous	0.469	Likely Benign	-6.42	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.31	Benign	0.02	Affected	3.37	29	0.2992	0.5728		0	-2	3.1	-72.06	165.3	110.8	0.0	0.0	-0.1	0.0		X						Potentially Pathogenic	The carboxylate group of Glu419, located on an α helix (res. Met414-Glu436), forms a salt bridge with the side chain of either Arg716 or Lys418 from an opposing helix (res. Pro713-Arg726). The backbone amide group of Glu419 does not form H-bonds, resulting in a slight bend in the α helix. Thus, although glycine is known as an “α helix breaker,” the residue swap does not disrupt the continuity or integrity of the α helix. However, because Gly419 cannot form a salt bridge with the guanidinium group of the Arg716 side chain, the C2-GAP domain tertiary structure could be compromised during folding.
c.1265A>G	E422G 2D 3DClick to see structure in 3D Viewer AISynGAP1 E422G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split assessment: benign predictions come from REVEL, premPS, and FATHMM, while pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Uncertain results are provided by FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy analyses indicate that the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, predicts a likely pathogenic effect, whereas AlphaMissense‑Optimized remains inconclusive and Foldetta shows no definitive stability change. Overall, the majority of evidence points toward a pathogenic impact for E422G, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.426709	Uncertain	0.965	0.255	0.000											-11.468	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	1.13	Ambiguous	0.0	1.25	Ambiguous	1.19	Ambiguous	0.39	Likely Benign	0.488	Likely Benign	-6.38	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.31	Benign	0.01	Affected			0.2440	0.4184		0	-2	3.1	-72.06
c.1322T>G	V441G 2D 3DClick to see structure in 3D Viewer AISynGAP1 variant V441G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into three groups: benign predictions come from REVEL, FoldX, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b; the remaining tools (Rosetta, Foldetta, premPS, AlphaMissense‑Default) give uncertain results. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized remains benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) favors pathogenic, and Foldetta is inconclusive. Taken together, the majority of evidence points to a benign effect, but the SGM Consensus and several individual pathogenic predictors introduce uncertainty. Therefore, the variant is most likely benign based on the overall prediction landscape, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.161087	Structured	0.259875	Uncertain	0.918	0.249	0.000											-12.380	Likely Pathogenic	0.478	Ambiguous	Likely Benign	0.18	Likely Benign	0.0	1.25	Ambiguous	0.72	Ambiguous	0.95	Ambiguous	0.273	Likely Benign	-5.88	Deleterious	0.841	Possibly Damaging	0.997	Probably Damaging	3.41	Benign	0.24	Tolerated			0.1664	0.1715		-1	-3	-4.6	-42.08
c.1330A>C	K444Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 K444Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL, SIFT, and FATHMM; pathogenic predictions from premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (majority vote) is pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for K444Q, and this conclusion does not conflict with any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.203355	Structured	0.262172	Uncertain	0.955	0.213	0.000											-12.876	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.34	Ambiguous	0.0	1.36	Ambiguous	1.35	Ambiguous	1.04	Destabilizing	0.382	Likely Benign	-3.82	Deleterious	0.998	Probably Damaging	0.997	Probably Damaging	3.43	Benign	0.07	Tolerated			0.4112	0.1057		1	1	0.4	-0.04
c.1337A>G	E446G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E446G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM. The majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and Foldetta. Predictions that are uncertain or inconclusive are AlphaMissense‑Optimized, Rosetta, and premPS. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is Pathogenic. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.276479	Uncertain	0.940	0.216	0.000											-11.457	Likely Pathogenic	0.866	Likely Pathogenic	Ambiguous	2.62	Destabilizing	0.7	1.63	Ambiguous	2.13	Destabilizing	0.83	Ambiguous	0.510	Likely Pathogenic	-6.42	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.24	Benign	0.00	Affected			0.2665	0.5202		0	-2	3.1	-72.06
c.1393C>A	L465I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L465I missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score classifies the variant as benign, whereas the Foldetta stability assessment is uncertain. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive due to a 2‑to‑2 split. Overall, the evidence is mixed; the balance of predictions leans toward a benign interpretation, and this does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.346032	Structured	0.319240	Uncertain	0.956	0.202	0.000											-9.672	Likely Pathogenic	0.770	Likely Pathogenic	Likely Benign	1.21	Ambiguous	0.1	1.27	Ambiguous	1.24	Ambiguous	0.78	Ambiguous	0.258	Likely Benign	-1.99	Neutral	0.998	Probably Damaging	0.997	Probably Damaging	2.54	Benign	0.08	Tolerated			0.0967	0.3539		2	2	0.7	0.00
c.1393C>T	L465F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L465F is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL and Rosetta, whereas the majority of tools predict a pathogenic impact: FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Two tools (Foldetta and premPS) give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus also pathogenic, and Foldetta remains uncertain. Overall, the consensus of high‑confidence predictors points to a pathogenic effect for L465F. This conclusion is not contradicted by ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.346032	Structured	0.319240	Uncertain	0.956	0.202	0.000											-12.626	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	3.11	Destabilizing	0.7	0.05	Likely Benign	1.58	Ambiguous	0.52	Ambiguous	0.432	Likely Benign	-3.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.44	Pathogenic	0.01	Affected			0.0771	0.2759		2	0	-1.0	34.02
c.1400A>T	D467V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D467V missense variant is not reported in ClinVar or gnomAD. Prediction tools cluster into two groups: benign predictions come from Rosetta and premPS, while the majority—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—label the change as pathogenic. Two tools, FoldX and Foldetta, give uncertain results. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus indicates likely pathogenic, and Foldetta remains uncertain. Overall, the consensus of high‑confidence predictors points to a pathogenic effect, and this conclusion is consistent with the absence of any ClinVar annotation or gnomAD observation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.329932	Uncertain	0.940	0.246	0.000											-15.041	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	1.24	Ambiguous	0.1	0.08	Likely Benign	0.66	Ambiguous	0.02	Likely Benign	0.893	Likely Pathogenic	-8.70	Deleterious	0.997	Probably Damaging	0.997	Probably Damaging	-1.28	Pathogenic	0.02	Affected			0.0644	0.5274		-2	-3	7.7	-15.96
c.1421A>T	D474V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D474V missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that indicate a benign effect include Rosetta, Foldetta, and premPS, whereas the majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). FoldX is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as benign. Overall, the balance of evidence favors a pathogenic classification, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.373433	Uncertain	0.864	0.255	0.000											-12.999	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	0.77	Ambiguous	0.0	0.18	Likely Benign	0.48	Likely Benign	0.18	Likely Benign	0.866	Likely Pathogenic	-7.69	Deleterious	0.998	Probably Damaging	0.997	Probably Damaging	-1.30	Pathogenic	0.04	Affected			0.0694	0.4510		-2	-3	7.7	-15.96
c.1465C>A	L489I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L489I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into three groups: benign predictions come from REVEL, PROVEAN, SIFT, and AlphaMissense‑Optimized; pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; the remaining methods (FoldX, Rosetta, Foldetta, premPS, ESM1b, AlphaMissense‑Default) yield uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is indeterminate due to a tie between pathogenic and benign signals, and Foldetta reports an uncertain stability change. Overall, the preponderance of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.191378	Structured	0.326126	Uncertain	0.949	0.234	0.125											-7.333	In-Between	0.342	Ambiguous	Likely Benign	1.01	Ambiguous	0.0	0.52	Ambiguous	0.77	Ambiguous	0.90	Ambiguous	0.490	Likely Benign	-1.55	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	-1.42	Pathogenic	0.21	Tolerated			0.1069	0.4080		2	2	0.7	0.00
c.1465C>T	L489F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L489F is listed in ClinVar with an uncertain significance (ClinVar ID 522018.0) and is present in the gnomAD database (gnomAD ID 6‑33438497‑C‑T). In silico prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report a pathogenic outcome, while no tool predicts a benign effect. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. No prediction or folding‑stability result is missing or ambiguous. **Thus, the variant is most likely pathogenic based on the collective predictions, and this does not contradict the ClinVar uncertain status.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.191378	Structured	0.326126	Uncertain	0.949	0.234	0.125					Uncertain		2	6-33438497-C-T	1	6.20e-7	-12.066	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	1.72	Ambiguous	0.5	1.14	Ambiguous	1.43	Ambiguous	0.56	Ambiguous	0.724	Likely Pathogenic	-3.76	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.51	Pathogenic	0.01	Affected	3.37	35	0.0791	0.3729		2	0	-1.0	34.02	246.4	-17.8	0.0	0.0	0.6	0.1						X		Potentially Benign	The iso-butyl side chain of Leu489, located in the α-helix (res. Leu489-Glu519) within an inter-helix space of four helices (res. Ala461-Phe476, res. Val441-Ser457, and res. Met414-Glu436), packs with hydrophobic residues (e.g., Cys432, Ala448, Lys444, Ala493, Val447, Met468) in the inter-helix space. In the variant simulations, the phenyl ring of the Phe489 side chain can also pack favorably in the hydrophobic region. However, due to the size difference, the aromatic side chain of Phe489 tends to reposition to escape the tight region to accommodate the larger side chain, stacking with Lys444. Although no apparent negative changes are observed during the variant simulation, the size difference between the swapped residues could affect the protein folding process.
c.1472C>T	T491I 2D AIThe SynGAP1 missense variant T491I is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only premPS; all other evaluated algorithms (SGM‑Consensus, REVEL, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact, while FoldX is uncertain and therefore not counted in either group. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized reports a pathogenic change, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Based on the collective predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.064632	Structured	0.325158	Uncertain	0.929	0.188	0.125											-12.525	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	1.48	Ambiguous	1.8	3.73	Destabilizing	2.61	Destabilizing	0.49	Likely Benign	0.915	Likely Pathogenic	-5.89	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.42	Pathogenic	0.00	Affected			0.0898	0.4942		0	-1	5.2	12.05
c.1482A>G	I494M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I494M missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. The remaining tools—Rosetta, Foldetta, premPS, and AlphaMissense‑Default—return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the balance of evidence leans toward pathogenicity, with a majority of tools predicting a deleterious effect. This conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.155435	Structured	0.353330	Uncertain	0.941	0.157	0.000											-8.223	Likely Pathogenic	0.356	Ambiguous	Likely Benign	0.35	Likely Benign	0.2	1.98	Ambiguous	1.17	Ambiguous	0.98	Ambiguous	0.542	Likely Pathogenic	-2.25	Neutral	1.000	Probably Damaging	0.997	Probably Damaging	-1.15	Pathogenic	0.23	Tolerated			0.0676	0.1789		2	1	-2.6	18.03
c.1516C>A	L506I 2D AIThe SynGAP1 missense variant L506I is not reported in ClinVar and is absent from gnomAD. Consensus from standard in‑silico predictors shows a split: benign calls come from REVEL, PROVEAN, and AlphaMissense‑Optimized, whereas pathogenic calls arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. Uncertain results are reported by FoldX, premPS, and AlphaMissense‑Default. High‑accuracy assessments give a pathogenic verdict from Foldetta (a combined FoldX‑MD/Rosetta stability analysis) and from the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). AlphaMissense‑Optimized, however, predicts benign. Overall, the majority of reliable tools and the high‑accuracy methods favor a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.034884	Structured	0.279180	Uncertain	0.924	0.196	0.000											-10.386	Likely Pathogenic	0.501	Ambiguous	Likely Benign	1.73	Ambiguous	1.0	2.85	Destabilizing	2.29	Destabilizing	0.98	Ambiguous	0.365	Likely Benign	-1.99	Neutral	0.998	Probably Damaging	0.997	Probably Damaging	1.65	Pathogenic	0.01	Affected			0.0745	0.2033		2	2	0.7	0.00
c.1516C>T	L506F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L506F is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact; premPS and AlphaMissense‑Optimized are inconclusive. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is uncertain, the SGM Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, which is consistent with its ClinVar “Uncertain” classification and does not contradict the available data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.034884	Structured	0.279180	Uncertain	0.924	0.196	0.000					Uncertain		1				-11.262	Likely Pathogenic	0.883	Likely Pathogenic	Ambiguous	4.92	Destabilizing	0.8	5.76	Destabilizing	5.34	Destabilizing	0.91	Ambiguous	0.464	Likely Benign	-3.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.62	Pathogenic	0.01	Affected	3.37	35	0.0566	0.1471		0	2	-1.0	34.02
c.1529T>C	I510T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I510T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized. All other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and Foldetta—classify the variant as pathogenic, while Rosetta remains uncertain. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta predicts pathogenic. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.250630	Uncertain	0.945	0.273	0.000											-9.993	Likely Pathogenic	0.701	Likely Pathogenic	Likely Benign	3.08	Destabilizing	0.2	1.99	Ambiguous	2.54	Destabilizing	1.95	Destabilizing	0.914	Likely Pathogenic	-3.63	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.43	Pathogenic	0.00	Affected			0.0960	0.0440		0	-1	-5.2	-12.05
c.1537T>A	F513I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F513I is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools largely converge on a deleterious effect: SIFT is the sole benign caller, whereas REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. Grouping by consensus, the single benign prediction (SIFT) is outweighed by the 13 pathogenic calls. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a pathogenic effect; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts a pathogenic outcome. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.250651	Uncertain	0.949	0.269	0.000											-12.003	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	3.42	Destabilizing	0.4	2.18	Destabilizing	2.80	Destabilizing	1.12	Destabilizing	0.766	Likely Pathogenic	-5.70	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-1.24	Pathogenic	0.22	Tolerated			0.1473	0.1766		1	0	1.7	-34.02
c.1580A>T	D527V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D527V missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a pathogenic effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that are uncertain (FoldX, Rosetta, Foldetta, premPS) provide no definitive evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, while Foldetta remains uncertain. Overall, the majority of reliable predictors classify the variant as pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists. Thus, based on current computational evidence, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.021908	Uncertain	0.913	0.408	0.000											-16.844	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	0.71	Ambiguous	0.7	0.84	Ambiguous	0.78	Ambiguous	-0.55	Ambiguous	0.938	Likely Pathogenic	-8.78	Deleterious	0.998	Probably Damaging	0.997	Probably Damaging	-2.40	Pathogenic	0.00	Affected			0.0659	0.3984		-2	-3	7.7	-15.96
c.1601C>G	S534C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S534C is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include REVEL, FoldX, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta is uncertain, so both are treated as unavailable. No other high‑accuracy predictions are available. Overall, the evidence is evenly split between benign and pathogenic predictions, leaving the variant’s clinical significance inconclusive. There is no ClinVar status to contradict this balanced prediction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.167087	Structured	0.032173	Uncertain	0.860	0.362	0.000											-8.077	Likely Pathogenic	0.247	Likely Benign	Likely Benign	0.18	Likely Benign	0.1	0.90	Ambiguous	0.54	Ambiguous	0.56	Ambiguous	0.308	Likely Benign	-4.05	Deleterious	0.998	Probably Damaging	0.997	Probably Damaging	3.25	Benign	0.00	Affected			0.0984	0.4861		0	-1	3.3	16.06
c.1608G>C	L536F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L536F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only Rosetta. Those that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus. Predictions that are uncertain or inconclusive are FoldX, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of reliable tools predict a pathogenic impact, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.137348	Structured	0.042188	Uncertain	0.931	0.341	0.000											-10.316	Likely Pathogenic	0.851	Likely Pathogenic	Ambiguous	1.31	Ambiguous	0.5	0.40	Likely Benign	0.86	Ambiguous	0.70	Ambiguous	0.724	Likely Pathogenic	-3.90	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.36	Pathogenic	0.01	Affected			0.0874	0.2804		2	0	-1.0	34.02
c.1608G>T	L536F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L536F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only Rosetta. Those that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus. Predictions that are uncertain or inconclusive are FoldX, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of reliable tools predict a pathogenic impact, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.137348	Structured	0.042188	Uncertain	0.931	0.341	0.000											-10.316	Likely Pathogenic	0.851	Likely Pathogenic	Ambiguous	1.31	Ambiguous	0.5	0.40	Likely Benign	0.86	Ambiguous	0.70	Ambiguous	0.722	Likely Pathogenic	-3.90	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.36	Pathogenic	0.01	Affected			0.0874	0.2804		2	0	-1.0	34.02
c.1624A>G	N542D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N542D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only SIFT, whereas the majority of tools (REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic impact; Rosetta and Foldetta are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Taken together, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.053060	Structured	0.026143	Uncertain	0.953	0.331	0.000											-13.269	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	2.13	Destabilizing	0.3	1.75	Ambiguous	1.94	Ambiguous	1.05	Destabilizing	0.796	Likely Pathogenic	-4.51	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.40	Pathogenic	0.08	Tolerated			0.1664	0.3176		2	1	0.0	0.98
c.1626C>A	N542K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N542K is not reported in ClinVar and has no entries in gnomAD. Prediction tools largely disagree: benign calls come from FoldX, SIFT, and Foldetta; pathogenic calls come from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools (Rosetta and premPS) give uncertain results. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, whereas Foldetta predicts benign. No prediction or stability result is missing or inconclusive. Overall, the majority of evidence (nine pathogenic vs three benign) points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.053060	Structured	0.026143	Uncertain	0.953	0.331	0.000											-11.967	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	-0.36	Likely Benign	0.1	0.53	Ambiguous	0.09	Likely Benign	0.75	Ambiguous	0.610	Likely Pathogenic	-5.33	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.23	Pathogenic	0.10	Tolerated			0.1870	0.4349		1	0	-0.4	14.07
c.1626C>G	N542K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N542K is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, SIFT, and Foldetta. Those that predict a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools (Rosetta and premPS) returned uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also pathogenic, while Foldetta predicts benign stability. No prediction or folding result is missing or inconclusive. Overall, the majority of evidence (nine pathogenic vs. three benign) indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.053060	Structured	0.026143	Uncertain	0.953	0.331	0.000											-11.967	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	-0.36	Likely Benign	0.1	0.53	Ambiguous	0.09	Likely Benign	0.75	Ambiguous	0.610	Likely Pathogenic	-5.33	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.23	Pathogenic	0.10	Tolerated			0.1870	0.4349		1	0	-0.4	14.07
c.1631G>A	R544Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R544Q is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33438874‑G‑A). Prediction tools that classify the change as benign include FoldX, PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that predict pathogenicity are REVEL, premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Foldetta and Rosetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta remains uncertain. Overall, the majority of evidence points toward a pathogenic effect, which is not contradictory to the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.038858	Structured	0.016004	Uncertain	0.967	0.333	0.000					Uncertain		1	6-33438874-G-A	1	6.20e-7	-10.281	Likely Pathogenic	0.596	Likely Pathogenic	Likely Benign	0.19	Likely Benign	0.2	0.87	Ambiguous	0.53	Ambiguous	1.40	Destabilizing	0.542	Likely Pathogenic	-2.41	Neutral	1.000	Probably Damaging	0.997	Probably Damaging	-1.40	Pathogenic	0.09	Tolerated	3.37	35	0.2103	0.1959		1	1	1.0	-28.06
c.1633A>G	M545V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M545V is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include SIFT and Rosetta, while a majority of tools predict a pathogenic outcome: PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus. Tools with inconclusive results (FoldX, Foldetta, premPS, ESM1b) are considered unavailable for interpretation. High‑accuracy methods specifically indicate pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta is uncertain. Overall, the preponderance of evidence points to a pathogenic effect for M545V. This conclusion is not contradicted by ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.012875	Uncertain	0.955	0.311	0.000											-7.481	In-Between	0.979	Likely Pathogenic	Likely Pathogenic	0.91	Ambiguous	0.1	0.33	Likely Benign	0.62	Ambiguous	0.94	Ambiguous	0.688	Likely Pathogenic	-3.54	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.26	Pathogenic	0.34	Tolerated			0.2454	0.2953		2	1	2.3	-32.06
c.1647G>C	L549F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L549F is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include Rosetta, premPS, and SIFT, whereas a majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX and Foldetta give uncertain results. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, which is consistent with its ClinVar “Uncertain” classification and does not contradict the available data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.007921	Uncertain	0.955	0.281	0.000					Uncertain		1				-11.634	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.80	Ambiguous	0.3	0.27	Likely Benign	0.54	Ambiguous	0.49	Likely Benign	0.514	Likely Pathogenic	-3.42	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.29	Pathogenic	0.14	Tolerated			0.0724	0.1859		2	0	-1.0	34.02
c.1647G>T	L549F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L549F is not reported in ClinVar and is absent from gnomAD. Benign predictions come from Rosetta, premPS, and SIFT, whereas pathogenic predictions are made by REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; the SGM‑Consensus score indicates likely pathogenic, while FoldX and Foldetta are uncertain. High‑accuracy tools specifically: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.007921	Uncertain	0.955	0.281	0.000											-11.634	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.80	Ambiguous	0.3	0.27	Likely Benign	0.54	Ambiguous	0.49	Likely Benign	0.514	Likely Pathogenic	-3.42	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.29	Pathogenic	0.14	Tolerated			0.0724	0.1859		2	0	-1.0	34.02
c.1666A>G	N556D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N556D is not reported in ClinVar (ClinVar status: None) and has no entry in gnomAD (gnomAD ID: None). Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, premPS, SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. With two of the three high‑accuracy tools indicating benign and an equal split among the broader set of predictors, the variant is most likely benign. This conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.015078	Structured	0.008655	Uncertain	0.925	0.225	0.000											-6.787	Likely Benign	0.704	Likely Pathogenic	Likely Benign	0.41	Likely Benign	0.0	0.39	Likely Benign	0.40	Likely Benign	0.33	Likely Benign	0.546	Likely Pathogenic	-3.19	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.33	Pathogenic	0.08	Tolerated			0.1817	0.1625		2	1	0.0	0.98
c.1668C>A	N556K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N556K is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include FoldX, Rosetta, premPS, and SIFT, whereas the remaining tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized) predict it to be pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions support a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Thus, the variant is most likely pathogenic based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.015078	Structured	0.008655	Uncertain	0.925	0.225	0.000											-10.017	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	0.10	Likely Benign	0.1	0.14	Likely Benign	0.12	Likely Benign	0.40	Likely Benign	0.510	Likely Pathogenic	-4.48	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-1.08	Pathogenic	0.14	Tolerated			0.2024	0.2240		1	0	-0.4	14.07
c.1668C>G	N556K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N556K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from FoldX, Rosetta, premPS, and SIFT; pathogenic predictions from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support this dichotomy: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign effect. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion is consistent with the absence of ClinVar annotation (i.e., no conflicting benign classification). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.015078	Structured	0.008655	Uncertain	0.925	0.225	0.000											-10.017	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	0.10	Likely Benign	0.1	0.14	Likely Benign	0.12	Likely Benign	0.40	Likely Benign	0.510	Likely Pathogenic	-4.48	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-1.08	Pathogenic	0.14	Tolerated			0.2024	0.2240		1	0	-0.4	14.07
c.1677C>G	C559W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change C559W is not listed in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM; pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is Uncertain, SGM Consensus is Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is Benign. Overall, seven of the twelve evaluated tools predict pathogenicity versus six benign, giving a slight majority toward a deleterious effect. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.016021	Structured	0.010460	Uncertain	0.842	0.204	0.000											-12.765	Likely Pathogenic	0.921	Likely Pathogenic	Ambiguous	-0.19	Likely Benign	0.0	0.01	Likely Benign	-0.09	Likely Benign	0.44	Likely Benign	0.274	Likely Benign	-8.54	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.42	Benign	0.03	Affected			0.2492	0.2135		-8	-2	-3.4	83.07
c.1681T>A	F561I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F561I is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (variant ID 6‑33440733‑T‑A). Prediction tools that agree on a benign effect include only SIFT. All other evaluated predictors—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.018013	Uncertain	0.903	0.196	0.000								6-33440733-T-A	1	6.32e-7	-11.708	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	3.82	Destabilizing	0.1	2.13	Destabilizing	2.98	Destabilizing	1.46	Destabilizing	0.710	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-1.06	Pathogenic	0.09	Tolerated	3.37	35	0.1825	0.1925		0	1	1.7	-34.02
c.1687A>T	R563W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R563W is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments show that AlphaMissense‑Optimized is inconclusive, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. No evidence from the uncertain tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) supports either outcome. Overall, the balance of evidence favors a pathogenic classification for R563W, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.039760	Structured	0.031987	Uncertain	0.876	0.209	0.000											-12.454	Likely Pathogenic	0.854	Likely Pathogenic	Ambiguous	1.25	Ambiguous	0.1	0.79	Ambiguous	1.02	Ambiguous	0.34	Likely Benign	0.302	Likely Benign	-6.75	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.42	Benign	0.01	Affected			0.1378	0.2088		2	-3	3.6	30.03
c.1688G>C	R563T 2D 3DClick to see structure in 3D Viewer AISynGAP1 R563T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, SIFT, and FATHMM, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The remaining tools—FoldX, Rosetta, ESM1b, AlphaMissense‑Optimized, and Foldetta—give uncertain or inconclusive results. High‑accuracy methods provide the following: AlphaMissense‑Optimized is unavailable; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic; Foldetta is unavailable. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.039760	Structured	0.031987	Uncertain	0.876	0.209	0.000											-7.088	In-Between	0.913	Likely Pathogenic	Ambiguous	1.13	Ambiguous	0.1	0.77	Ambiguous	0.95	Ambiguous	0.18	Likely Benign	0.307	Likely Benign	-4.77	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.49	Benign	0.23	Tolerated			0.2115	0.3148		-1	-1	3.8	-55.08
c.1705T>A	F569I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F569I is not listed in ClinVar and is absent from gnomAD. Across the available in‑silico predictors, every tool examined—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classifies the substitution as pathogenic. No predictor reports a benign outcome, so the benign group is empty. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a Likely Pathogenic verdict; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also indicates pathogenicity. Consequently, the variant is most likely pathogenic, and this prediction does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024393	Structured	0.054289	Uncertain	0.941	0.242	0.000											-15.362	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	3.75	Destabilizing	0.2	4.23	Destabilizing	3.99	Destabilizing	1.51	Destabilizing	0.903	Likely Pathogenic	-5.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-1.31	Pathogenic	0.01	Affected			0.1950	0.1973		1	0	1.7	-34.02
c.1717C>T	R573W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R573W is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that agree on a pathogenic effect include REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools with uncertain or inconclusive results are Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta yields an uncertain stability change. Overall, the majority of evidence points to a pathogenic effect, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.032433	Uncertain	0.934	0.235	0.000					Conflicting		8				-14.078	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	2.37	Destabilizing	0.7	0.57	Ambiguous	1.47	Ambiguous	0.88	Ambiguous	0.758	Likely Pathogenic	-6.94	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.48	Pathogenic	0.00	Affected	3.37	35	0.1179	0.2643		2	-3	3.6	30.03	257.6	39.0	0.1	0.0	0.2	0.0	X	X						Potentially Pathogenic	The guanidinium group of Arg573, located in an α-helix (res. Arg563-Glu578), forms a salt bridge with the carboxylate groups of Glu582 and/or Asp586 from a nearby α-helix (res. Glu582-Met603) in the WT simulations. Additionally, the Arg573 side chain stacks planarly with the aromatic phenol ring of Tyr665 and hydrogen bonds with the hydroxyl group of Ser668 from another α-helix (res. Ser641-Ser668). In the variant simulations, the indole ring of the Trp573 side chain is unable to maintain the same level of coordination as the positively charged Arg573 side chain. Indeed, Trp573 is seen hydrogen bonding only briefly with the carboxylate group of Glu582. Consequently, the integrity of the opposing α-helix end (res. Glu582-Met603) is weakened. Overall, the residue swap has the potential to substantially affect the tertiary structure assembly during the protein folding process.
c.1741C>T	R581W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R581W is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include only Rosetta, whereas the remaining pathogenic‑predicating tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—consistently classify the variant as deleterious. Uncertain or inconclusive results come from FoldX, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain”; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Pathogenic”; and Foldetta remains “Uncertain.” Overall, the preponderance of evidence points to a pathogenic impact, which contrasts with the ClinVar designation of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.029544	Uncertain	0.829	0.236	0.000					Uncertain		2				-12.855	Likely Pathogenic	0.920	Likely Pathogenic	Ambiguous	1.32	Ambiguous	0.1	-0.32	Likely Benign	0.50	Ambiguous	0.68	Ambiguous	0.678	Likely Pathogenic	-6.79	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.37	Pathogenic	0.01	Affected	3.37	34	0.1142	0.3043		2	-3	3.6	30.03	257.8	36.0	0.1	0.1	0.1	0.3	X	X						Potentially Pathogenic	Arg581 is located on a short α-α loop between two α helices (res. Arg563-Glu578 and res. Glu582-Ser604). In the WT simulations, the guanidinium group of Arg581 forms salt bridges with the carboxylate groups of Asp583 within the same helix, as well as with Glu478 and/or Glu480 in a slightly α-helical loop (res. Glu478-Thr488) preceding another α helix (res. Ala461-Phe476).In the variant simulations, the neutral indole ring of the Trp581 side chain cannot form any of these salt bridges. Instead, it packs hydrophobically against Met477 and Ile587 without forming any direct hydrogen bonds. The tendency of the loop (res. Asp477-Thr488) to acquire an α-helical structure seems to marginally increase, potentially due to Trp581's inability to coordinate stable hydrogen bonds with the loop residues (e.g., Glu478-Arg581 salt bridge). Additionally, the residue swap could weaken the tertiary structure assembly and negatively affect the overall protein folding process.
c.1751T>G	I584S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I584S missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on pathogenicity include SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tool predicts a benign effect. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta as pathogenic. No contradictory evidence is present. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not conflict with the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.059222	Structured	0.046673	Uncertain	0.846	0.244	0.000											-13.379	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous	3.15	Destabilizing	0.1	2.53	Destabilizing	2.84	Destabilizing	1.70	Destabilizing	0.710	Likely Pathogenic	-5.54	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.18	Pathogenic	0.03	Affected			0.2391	0.0858		-1	-2	-5.3	-26.08
c.1762C>A	L588I 2D AISynGAP1 missense variant L588I has no ClinVar entry and is not reported in gnomAD. Prediction tools that classify the variant as benign include PROVEAN. Those that predict pathogenicity are SGM‑Consensus, REVEL, FoldX, Foldetta, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain results come from Rosetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of evidence supports a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.038042	Structured	0.082229	Uncertain	0.887	0.214	0.000											-12.454	Likely Pathogenic	0.874	Likely Pathogenic	Ambiguous	2.54	Destabilizing	1.2	1.80	Ambiguous	2.17	Destabilizing	0.88	Ambiguous	0.607	Likely Pathogenic	-1.99	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	-1.27	Pathogenic	0.04	Affected			0.0949	0.2433		2	2	0.7	0.00
c.1762C>T	L588F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L588F is reported in gnomAD (variant ID 6‑33440814‑C‑T) but has no ClinVar entry. Across the available in‑silico predictors, every tool examined classifies the substitution as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return pathogenic or likely pathogenic scores. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is pathogenic. Because every available prediction converges on a deleterious effect and there is no ClinVar annotation to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.038042	Structured	0.082229	Uncertain	0.887	0.214	0.000								6-33440814-C-T			-14.050	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	2.90	Destabilizing	0.2	2.55	Destabilizing	2.73	Destabilizing	1.12	Destabilizing	0.736	Likely Pathogenic	-3.98	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.38	Pathogenic	0.04	Affected	3.38	34	0.0816	0.2007		0	2	-1.0	34.02
c.1777C>A	L593I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L593I missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are FoldX, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Predictions that are uncertain are Rosetta, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign effect. The variant’s predicted benign status does not contradict its ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.009728	Structured	0.110534	Uncertain	0.941	0.151	0.000											-8.617	Likely Pathogenic	0.448	Ambiguous	Likely Benign	2.16	Destabilizing	0.3	0.76	Ambiguous	1.46	Ambiguous	0.39	Likely Benign	0.169	Likely Benign	-1.59	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	3.14	Benign	0.17	Tolerated			0.1071	0.3582		2	2	0.7	0.00
c.1777C>T	L593F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L593F is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, and FATHMM, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Predictions that are inconclusive—FoldX, Foldetta, premPS, and AlphaMissense‑Optimized—are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009728	Structured	0.110534	Uncertain	0.941	0.151	0.000											-12.723	Likely Pathogenic	0.954	Likely Pathogenic	Ambiguous	1.46	Ambiguous	0.4	0.24	Likely Benign	0.85	Ambiguous	0.62	Ambiguous	0.304	Likely Benign	-3.78	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	2.95	Benign	0.01	Affected			0.0884	0.2631		2	0	-1.0	34.02
c.1780T>A	F594I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F594I is not reported in ClinVar and has no entries in gnomAD. In silico assessment shows that all evaluated pathogenicity predictors—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—classify the substitution as pathogenic, while FoldX, Rosetta, and Foldetta provide inconclusive results. High‑accuracy tools further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta remains uncertain. Consequently, the overwhelming majority of predictions point to a pathogenic impact. The variant is therefore most likely pathogenic, and this assessment does not contradict any ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009187	Structured	0.120166	Uncertain	0.946	0.147	0.000											-11.271	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	1.93	Ambiguous	0.1	1.67	Ambiguous	1.80	Ambiguous	1.61	Destabilizing	0.935	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-1.91	Pathogenic	0.02	Affected			0.1694	0.1925		1	0	1.7	-34.02
c.1789T>A	F597I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F597I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect. Benign predictions: none. Pathogenic predictions: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. All available evidence points to a pathogenic effect. Therefore, the variant is most likely pathogenic, and this conclusion is consistent with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.010926	Structured	0.142961	Uncertain	0.944	0.151	0.000											-13.674	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	3.62	Destabilizing	0.9	2.15	Destabilizing	2.89	Destabilizing	1.45	Destabilizing	0.951	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-2.18	Pathogenic	0.01	Affected			0.2008	0.1815		1	0	1.7	-34.02
c.1802C>G	A601G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A601G missense variant is listed in gnomAD (ID 6‑33440854‑C‑G) but has no ClinVar entry. Prediction tools that agree on a benign effect are FATHMM and AlphaMissense‑Optimized; those that agree on a pathogenic effect are REVEL, FoldX, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. The high‑accuracy consensus methods give a pathogenic verdict: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also pathogenic. AlphaMissense‑Default and premPS are uncertain, and no evidence is available from other folding‑stability tools. Overall, the preponderance of evidence points to a pathogenic impact for A601G, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.008895	Structured	0.174517	Uncertain	0.955	0.156	0.000								6-33440854-C-G	1	6.19e-7	-11.772	Likely Pathogenic	0.543	Ambiguous	Likely Benign	2.03	Destabilizing	0.0	2.31	Destabilizing	2.17	Destabilizing	0.94	Ambiguous	0.511	Likely Pathogenic	-3.98	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	2.55	Benign	0.01	Affected	3.37	35	0.2337	0.4370		0	1	-2.2	-14.03
c.1816A>C	S606R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S606R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, and FATHMM, whereas a separate group predicts pathogenicity: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Tools with uncertain outcomes are Foldetta, premPS, and Rosetta. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic, and Foldetta remains inconclusive. Overall, the majority of high‑confidence predictions and the consensus vote indicate a pathogenic effect. Because ClinVar contains no entry for this variant, there is no contradiction between the computational evidence and clinical annotation. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.191720	Uncertain	0.875	0.247	0.000											-12.900	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.15	Likely Benign	0.4	1.80	Ambiguous	0.98	Ambiguous	0.82	Ambiguous	0.252	Likely Benign	-4.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	3.38	Benign	0.08	Tolerated			0.0819	0.2750		0	-1	-3.7	69.11
c.1816A>T	S606C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S606C is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign, and the SGM‑Consensus as Likely Pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overall distribution of predictions, the variant is most likely benign, although the SGM‑Consensus suggests pathogenicity; this does not contradict any ClinVar status because the variant is not yet classified in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.191720	Uncertain	0.875	0.247	0.000											-11.122	Likely Pathogenic	0.774	Likely Pathogenic	Likely Benign	-0.34	Likely Benign	0.0	-0.31	Likely Benign	-0.33	Likely Benign	0.49	Likely Benign	0.348	Likely Benign	-4.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	3.31	Benign	0.00	Affected			0.0986	0.4580		0	-1	3.3	16.06
c.1818T>A	S606R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S606R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, and FATHMM, whereas a separate group predicts pathogenicity: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Tools with uncertain outcomes are Foldetta, premPS, and Rosetta. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic, and Foldetta remains inconclusive. Overall, the majority of high‑confidence predictions and the consensus vote indicate a pathogenic effect. Because ClinVar contains no entry for this variant, there is no contradiction between the computational evidence and clinical annotation. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.191720	Uncertain	0.875	0.247	0.000											-12.900	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.15	Likely Benign	0.4	1.80	Ambiguous	0.98	Ambiguous	0.82	Ambiguous	0.246	Likely Benign	-4.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	3.38	Benign	0.08	Tolerated			0.0819	0.2750		0	-1	-3.7	69.11
c.1818T>G	S606R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S606R is not reported in ClinVar or gnomAD. Prediction tools that indicate a benign effect include REVEL, FoldX, SIFT, and FATHMM, whereas a majority predict pathogenicity: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain. High‑accuracy methods confirm the pathogenic trend: AlphaMissense‑Optimized is pathogenic, SGM Consensus is Likely Pathogenic, and Foldetta remains uncertain. Overall, the evidence points to the variant being most likely pathogenic, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.191720	Uncertain	0.875	0.247	0.000											-12.900	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.15	Likely Benign	0.4	1.80	Ambiguous	0.98	Ambiguous	0.82	Ambiguous	0.246	Likely Benign	-4.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	3.38	Benign	0.08	Tolerated			0.0819	0.2750		0	-1	-3.7	69.11
c.1819C>A	L607I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L607I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from SGM‑Consensus, REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default, while benign calls are made by PROVEAN and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Stability predictions from FoldX, Rosetta, and premPS are inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for L607I. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.194229	Uncertain	0.869	0.250	0.000											-12.061	Likely Pathogenic	0.644	Likely Pathogenic	Likely Benign	0.63	Ambiguous	0.1	1.25	Ambiguous	0.94	Ambiguous	0.82	Ambiguous	0.727	Likely Pathogenic	-1.99	Neutral	0.992	Probably Damaging	0.997	Probably Damaging	-1.54	Pathogenic	0.01	Affected			0.1079	0.3767		2	2	0.7	0.00
c.1819C>T	L607F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L607F is catalogued in gnomAD (6‑33440871‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all report pathogenic or likely pathogenic. Only FoldX predicts a benign outcome, while Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized are uncertain. High‑accuracy assessments show the SGM‑Consensus as likely pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for L607F, and this conclusion is not contradicted by ClinVar status (none). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.194229	Uncertain	0.869	0.250	0.000								6-33440871-C-T	1	6.19e-7	-13.654	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous	0.23	Likely Benign	0.1	1.20	Ambiguous	0.72	Ambiguous	0.61	Ambiguous	0.758	Likely Pathogenic	-3.98	Deleterious	0.998	Probably Damaging	0.997	Probably Damaging	-1.54	Pathogenic	0.01	Affected	3.37	35	0.0872	0.2816		0	2	-1.0	34.02
c.1822T>A	F608I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F608I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenic or likely pathogenic. The only tool with an inconclusive result is FoldX, which is listed as uncertain. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion is consistent with the absence of any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.106997	Structured	0.197190	Uncertain	0.891	0.247	0.000											-14.939	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	1.92	Ambiguous	0.1	2.14	Destabilizing	2.03	Destabilizing	1.24	Destabilizing	0.904	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-1.62	Pathogenic	0.00	Affected			0.2115	0.2361		1	0	1.7	-34.02
c.1828C>A	L610I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L610I is listed in gnomAD (ID 6‑33440880‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions arise from REVEL, polyPhen‑2 (HumDiv and HumVar) and FATHMM. Four tools are uncertain (FoldX, Foldetta, premPS, AlphaMissense‑Default). High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized scores benign, the SGM consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign, whereas Foldetta’s stability estimate is unavailable. Overall, the balance of evidence points to a benign effect for L610I, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.271506	Structured	0.209504	Uncertain	0.888	0.253	0.000								6-33440880-C-A	1	6.19e-7	-6.362	Likely Benign	0.389	Ambiguous	Likely Benign	1.50	Ambiguous	0.2	0.18	Likely Benign	0.84	Ambiguous	0.76	Ambiguous	0.544	Likely Pathogenic	-1.86	Neutral	0.992	Probably Damaging	0.997	Probably Damaging	-1.34	Pathogenic	0.15	Tolerated	3.37	35	0.0999	0.3219		2	2	0.7	0.00
c.1828C>T	L610F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L610F is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—all of which classify the variant as pathogenic. No tools predict a benign outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a pathogenic effect. Based on the consensus of these predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.209504	Uncertain	0.888	0.253	0.000											-13.244	Likely Pathogenic	0.808	Likely Pathogenic	Ambiguous	6.24	Destabilizing	1.1	3.40	Destabilizing	4.82	Destabilizing	0.68	Ambiguous	0.782	Likely Pathogenic	-3.92	Deleterious	0.998	Probably Damaging	0.997	Probably Damaging	-1.52	Pathogenic	0.01	Affected			0.0834	0.2816		2	0	-1.0	34.02
c.1856C>T	T619I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T619I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity unanimously classify the variant as pathogenic: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect; the remaining tools (FoldX, Rosetta, Foldetta, premPS) return uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is uncertain. Based on the consensus of pathogenic predictions and the lack of benign evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.219301	Structured	0.119723	Uncertain	0.929	0.237	0.000											-11.760	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	-1.06	Ambiguous	0.1	-1.35	Ambiguous	-1.21	Ambiguous	0.58	Ambiguous	0.735	Likely Pathogenic	-5.54	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.40	Pathogenic	0.03	Affected			0.0869	0.4377		0	-1	5.2	12.05
c.1862G>A	R621Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R621Q is listed in ClinVar (ID 578137.0) as benign and is present in gnomAD (variant ID 6‑33440914‑G‑A). Functional prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No evidence from FoldX, Rosetta, or Foldetta supports a benign outcome. Overall, the preponderance of predictions indicates a likely pathogenic effect, which contradicts the benign classification reported in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.084420	Uncertain	0.945	0.216	0.000					Likely Benign		1	6-33440914-G-A	19	1.18e-5	-14.682	Likely Pathogenic	0.910	Likely Pathogenic	Ambiguous	0.81	Ambiguous	0.1	1.13	Ambiguous	0.97	Ambiguous	1.35	Destabilizing	0.621	Likely Pathogenic	-3.98	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	2.82	Benign	0.01	Affected	3.37	35	0.2590	0.1963		1	1	1.0	-28.06	243.7	54.3	0.0	0.0	-0.4	0.2		X		X				Potentially Pathogenic	The guanidinium group of Arg621, located in an α helix (res. Glu617-Asn635), forms a salt bridge with Glu525 in a nearby loop and stacks with Leu635. In the variant simulations, the carboxamide side chain of Gln621, which can act as both a hydrogen bond acceptor and donor, also stacks with Leu635 but can only sporadically hydrogen bond with Glu525.Accordingly, the residue swap could affect the tertiary structure integrity by disrupting the salt bridge formation. Additionally, due to its location at the GAP-Ras interface, the residue swap could impact the complex formation with the GTPase, but this cannot be investigated using solvent-only simulations.
c.1865C>T	T622I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T622I is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign are Foldetta and premPS, whereas the remaining tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict it to be pathogenic; FoldX and Rosetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.071403	Uncertain	0.957	0.198	0.000											-13.276	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	-1.47	Ambiguous	0.1	0.67	Ambiguous	-0.40	Likely Benign	0.45	Likely Benign	0.905	Likely Pathogenic	-5.57	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.57	Pathogenic	0.00	Affected			0.0855	0.4926		0	-1	5.2	12.05
c.1867C>A	L623I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L623I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign calls come only from REVEL and PROVEAN, while pathogenic calls are made by FoldX, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (which is derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Uncertain results are reported by Rosetta and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic prediction: AlphaMissense‑Optimized is inconclusive, the SGM‑Consensus is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenicity. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.060667	Uncertain	0.962	0.211	0.000											-11.952	Likely Pathogenic	0.911	Likely Pathogenic	Ambiguous	3.15	Destabilizing	0.5	1.90	Ambiguous	2.53	Destabilizing	1.13	Destabilizing	0.398	Likely Benign	-1.99	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	1.63	Pathogenic	0.02	Affected			0.1109	0.3767		2	2	0.7	0.00
c.1867C>T	L623F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L623F is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN)—predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus predicts likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) yields an uncertain result. No predictions are missing or inconclusive. Based on the overwhelming agreement among pathogenic predictions and the lack of a benign signal, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.060667	Uncertain	0.962	0.211	0.000											-11.655	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	1.22	Ambiguous	0.2	0.92	Ambiguous	1.07	Ambiguous	0.57	Ambiguous	0.440	Likely Benign	-3.98	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	1.65	Pathogenic	0.02	Affected			0.0838	0.3016		2	0	-1.0	34.02
c.1873C>A	L625I 2D AIThe SynGAP1 missense variant L625I is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas a majority of tools (premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. Tools with uncertain or inconclusive results—FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized—are treated as unavailable. High‑accuracy assessments are likewise inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta is uncertain. Consequently, the overall evidence leans toward pathogenicity, with no conflict with ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.229226	Structured	0.045896	Uncertain	0.966	0.215	0.000											-11.713	Likely Pathogenic	0.866	Likely Pathogenic	Ambiguous	0.75	Ambiguous	0.6	0.72	Ambiguous	0.74	Ambiguous	1.09	Destabilizing	0.412	Likely Benign	-1.96	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	3.06	Benign	0.01	Affected			0.0864	0.3588		2	2	0.7	0.00
c.1873C>T	L625F 2D AIThe SynGAP1 missense variant L625F is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM. Tools that predict a pathogenic effect include SGM‑Consensus (Likely Pathogenic), Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Predictions that are uncertain or inconclusive are FoldX, premPS, and Foldetta. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts Likely Pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is Uncertain. Overall, the majority of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.229226	Structured	0.045896	Uncertain	0.966	0.215	0.000											-12.989	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	1.70	Ambiguous	1.3	2.26	Destabilizing	1.98	Ambiguous	0.74	Ambiguous	0.479	Likely Benign	-3.82	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.01	Benign	0.01	Affected			0.0586	0.2998		2	0	-1.0	34.02
c.1907T>G	F636C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F636C is reported in gnomAD (ID 6‑33440959‑T‑G) but has no ClinVar entry. Prediction tools largely agree on a deleterious effect: pathogenic calls come from REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Only FATHMM predicts a benign outcome; FoldX is uncertain and therefore not counted as evidence. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No prediction or stability result is missing or inconclusive. Based on the overwhelming majority of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.071525	Uncertain	0.913	0.264	0.000								6-33440959-T-G	3	1.86e-6	-13.287	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic	1.74	Ambiguous	0.1	2.65	Destabilizing	2.20	Destabilizing	1.22	Destabilizing	0.612	Likely Pathogenic	-7.67	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.40	Benign	0.04	Affected	3.37	34	0.2301	0.0830		-2	-4	-0.3	-44.04
c.2000T>A	I667N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I667N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized indicates pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. No prediction or folding stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.142424	Structured	0.083597	Uncertain	0.927	0.379	0.000											-15.730	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	2.89	Destabilizing	0.2	2.84	Destabilizing	2.87	Destabilizing	2.56	Destabilizing	0.572	Likely Pathogenic	-6.73	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	2.95	Benign	0.00	Affected			0.0841	0.0470		-2	-3	-8.0	0.94
c.2005A>T	N669Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N669Y is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include FoldX, FATHMM, and premPS. Those that predict a pathogenic effect comprise SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. With eight pathogenic predictions versus three benign, the overall evidence points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.142424	Structured	0.086615	Uncertain	0.872	0.380	0.000											-13.548	Likely Pathogenic	0.802	Likely Pathogenic	Ambiguous	0.45	Likely Benign	0.4	1.29	Ambiguous	0.87	Ambiguous	0.21	Likely Benign	0.546	Likely Pathogenic	-7.01	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.34	Benign	0.00	Affected			0.0666	0.4151		-2	-2	2.2	49.07
c.2060G>C	R687P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R687P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, whereas the remaining eleven tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also indicates pathogenicity. With the overwhelming majority of evidence pointing to a damaging effect and no conflicting ClinVar annotation, the variant is most likely pathogenic, and this assessment does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.054297	Structured	0.191060	Uncertain	0.914	0.259	0.000											-15.697	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.31	Destabilizing	0.3	6.63	Destabilizing	4.47	Destabilizing	0.89	Ambiguous	0.553	Likely Pathogenic	-6.12	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.87	Benign	0.01	Affected			0.1811	0.3159		0	-2	2.9	-59.07
c.2063A>G	E688G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E688G has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM. Those that predict a pathogenic effect include FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive predictions come from Foldetta, premPS, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as uncertain (treated as unavailable). Overall, the majority of reliable tools predict a deleterious effect. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.211124	Uncertain	0.947	0.223	0.000											-14.338	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	2.17	Destabilizing	0.5	1.44	Ambiguous	1.81	Ambiguous	0.86	Ambiguous	0.486	Likely Benign	-6.55	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.27	Benign	0.00	Affected			0.3059	0.4433		0	-2	3.1	-72.06
c.2114A>T	K705M 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K705M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, FoldX, Foldetta, premPS, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Uncertain results are reported by Rosetta and AlphaMissense‑Optimized. The high‑accuracy consensus (SGM‑Consensus) aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN and yields a pathogenic verdict (3/4 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the majority of evidence points toward a pathogenic impact, and this assessment does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.379324	Uncertain	0.922	0.364	0.000											-9.595	Likely Pathogenic	0.939	Likely Pathogenic	Ambiguous	-0.13	Likely Benign	0.0	0.53	Ambiguous	0.20	Likely Benign	0.17	Likely Benign	0.306	Likely Benign	-3.65	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.26	Benign	0.00	Affected			0.0724	0.3057		0	-1	5.8	3.02
c.2138C>A	P713Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P713Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, FoldX, Foldetta, and FATHMM, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). Uncertain calls are made by Rosetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments further highlight this discordance: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign effect. Overall, the majority of evidence leans toward a benign interpretation, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.393235	Uncertain	0.961	0.371	0.000											-10.253	Likely Pathogenic	0.875	Likely Pathogenic	Ambiguous	0.26	Likely Benign	0.0	-0.77	Ambiguous	-0.26	Likely Benign	0.95	Ambiguous	0.364	Likely Benign	-6.38	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.37	Benign	0.00	Affected			0.1225	0.3388		0	-1	-1.9	31.01
c.2152C>A	L718I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L718I is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus (Likely Pathogenic), FoldX, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Three tools (Foldetta, premPS, Rosetta) give uncertain results and are not considered evidence. High‑accuracy methods specifically show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Because the majority of reliable predictors (eight out of eleven) indicate pathogenicity, the variant is most likely pathogenic. This assessment does not contradict ClinVar, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.298791	Structured	0.438417	Uncertain	0.966	0.385	0.000											-10.560	Likely Pathogenic	0.615	Likely Pathogenic	Likely Benign	2.21	Destabilizing	0.2	1.37	Ambiguous	1.79	Ambiguous	0.89	Ambiguous	0.296	Likely Benign	-1.90	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	1.37	Pathogenic	0.00	Affected			0.0876	0.3206		2	2	0.7	0.00
c.2152C>T	L718F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L718F lies in the GAP domain. ClinVar has no entry for this variant, and it is not present in gnomAD. Prediction tools cluster into two groups: benign predictions are made only by REVEL, whereas the remaining tools (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity; premPS is uncertain and is not counted as evidence. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Based on the overwhelming consensus of these predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.298791	Structured	0.438417	Uncertain	0.966	0.385	0.000											-11.302	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	3.87	Destabilizing	0.2	2.64	Destabilizing	3.26	Destabilizing	0.78	Ambiguous	0.347	Likely Benign	-3.73	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	1.32	Pathogenic	0.00	Affected			0.0590	0.2979		2	0	-1.0	34.02
c.2176A>T	R726W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R726W has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show a split: benign calls from REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized, while pathogenic calls come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further reveal AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as benign. No prediction or stability result is missing or inconclusive. Overall, the majority of tools (seven) predict a benign effect, but the SGM‑Consensus and several high‑accuracy methods indicate pathogenicity, leaving the variant’s clinical significance uncertain. The predictions do not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.521092	Disordered	0.449098	Uncertain	0.888	0.513	0.625											-10.091	Likely Pathogenic	0.580	Likely Pathogenic	Likely Benign	0.46	Likely Benign	0.1	0.46	Likely Benign	0.46	Likely Benign	0.15	Likely Benign	0.217	Likely Benign	-3.72	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	2.57	Benign	0.01	Affected			0.1161	0.4252		2	-3	3.6	30.03
c.2177G>C	R726T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R726T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default; FoldX is uncertain. High‑accuracy methods give a consistent benign signal: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Based on the aggregate predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.521092	Disordered	0.449098	Uncertain	0.888	0.513	0.625											-5.249	Likely Benign	0.661	Likely Pathogenic	Likely Benign	0.82	Ambiguous	0.0	-0.11	Likely Benign	0.36	Likely Benign	-0.01	Likely Benign	0.200	Likely Benign	-0.90	Neutral	1.000	Probably Damaging	0.997	Probably Damaging	2.74	Benign	1.00	Tolerated			0.1685	0.4569		-1	-1	3.8	-55.08
c.2245C>G	R749G 2D AIThe SynGAP1 missense variant R749G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for R749G, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.626050	Binding	0.337	0.860	0.625											-3.045	Likely Benign	0.285	Likely Benign	Likely Benign										0.161	Likely Benign	-1.03	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.68	Benign	0.02	Affected			0.3690	0.4196		-3	-2	4.1	-99.14
c.2246G>T	R749L 2D AIThe SynGAP1 missense variant R749L is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools cluster around a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. The AlphaMissense‑Default score is uncertain, and no Foldetta stability assessment is available. High‑accuracy predictors that are available—AlphaMissense‑Optimized and the SGM‑Consensus—both support a benign classification. Consequently, the overall evidence points to the variant being most likely benign, and this assessment does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.626050	Binding	0.337	0.860	0.625											-3.926	Likely Benign	0.413	Ambiguous	Likely Benign										0.168	Likely Benign	-2.15	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.65	Benign	0.01	Affected			0.2106	0.5154		-3	-2	8.3	-43.03
c.2363C>G	S788C 2D AIThe SynGAP1 missense variant S788C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and AlphaMissense‑Optimized, while five tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM) predict a pathogenic outcome. Two tools (ESM1b and AlphaMissense‑Default) return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status because the variant has not yet been classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.956248	Disordered	0.573557	Binding	0.349	0.895	0.750											-7.935	In-Between	0.472	Ambiguous	Likely Benign										0.269	Likely Benign	-3.90	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.1393	0.6073		0	-1	3.3	16.06
c.2368A>C	T790P 2D AIThe SynGAP1 missense variant T790P has no ClinVar entry (ClinVar status: not reported) but is present in gnomAD (ID 6‑33442920‑A‑C). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of conventional tools (5 pathogenic vs 4 benign) lean toward a pathogenic interpretation, while the single high‑accuracy tool suggests benign. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this does not contradict the ClinVar status, which currently has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.964893	Disordered	0.509280	Binding	0.385	0.896	0.875								6-33442920-A-C			-3.564	Likely Benign	0.088	Likely Benign	Likely Benign										0.250	Likely Benign	-3.55	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.25	Pathogenic	0.01	Affected	3.64	6	0.2147	0.4748		-1	0	-0.9	-3.99
c.2369C>A	T790N 2D AIThe SynGAP1 missense variant T790N is listed in ClinVar with an “Uncertain” status and is present in the gnomAD database (ID 6‑33442921‑C‑A). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive and therefore unavailable, and Foldetta results are not reported. Overall, the majority of conventional tools (5 pathogenic vs. 4 benign) lean toward a pathogenic interpretation, while the single high‑accuracy tool suggests benign. The variant’s ClinVar status remains uncertain, so there is no contradiction with the current clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.964893	Disordered	0.509280	Binding	0.385	0.896	0.875					Conflicting		3	6-33442921-C-A	69	4.28e-5	-5.243	Likely Benign	0.276	Likely Benign	Likely Benign										0.103	Likely Benign	-2.54	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.27	Pathogenic	0.02	Affected	3.64	6	0.1446	0.4653		0	0	-2.8	13.00
c.2369C>T	T790I 2D AIThe SynGAP1 missense variant T790I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic. Foldetta, which would provide a protein‑folding stability estimate, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact. This conclusion does not contradict the ClinVar status, which currently has no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.964893	Disordered	0.509280	Binding	0.385	0.896	0.875											-3.556	Likely Benign	0.482	Ambiguous	Likely Benign										0.190	Likely Benign	-3.08	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.28	Pathogenic	0.01	Affected			0.0987	0.5431		0	-1	5.2	12.05
c.2443C>A	R815S 2D AISynGAP1 R815S is listed in ClinVar as Benign (ID 3645150.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. Two tools report uncertainty: ESM1b and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM Consensus as Benign, and Foldetta (combining FoldX‑MD and Rosetta) has no available result. Overall, the majority of predictions lean toward pathogenicity, whereas the consensus and high‑accuracy tools suggest benignity. Thus, the variant is most likely pathogenic based on the prevailing predictions, contradicting its ClinVar benign designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.394753	Structured	0.780568	Binding	0.278	0.907	0.250					Benign		1				-7.324	In-Between	0.950	Likely Pathogenic	Ambiguous										0.138	Likely Benign	-1.86	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.67	Benign	0.02	Affected			0.2937	0.4164		0	-1	3.7	-69.11
c.2443C>G	R815G 2D AISynGAP1 missense variant R815G is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that agree on benign effect include REVEL and FATHMM, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. Uncertain calls are made by ESM1b and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.394753	Structured	0.780568	Binding	0.278	0.907	0.250					Uncertain		1				-7.983	In-Between	0.854	Likely Pathogenic	Ambiguous										0.146	Likely Benign	-3.22	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.62	Benign	0.02	Affected	4.32	4	0.3481	0.4015		-3	-2	4.1	-99.14
c.2444G>T	R815L 2D AISynGAP1 missense variant R815L is listed in ClinVar (ID 2505666.0) with an uncertain significance annotation and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of tools indicates a pathogenic effect, which contrasts with the ClinVar uncertain classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.394753	Structured	0.780568	Binding	0.278	0.907	0.250					Uncertain		1				-8.546	Likely Pathogenic	0.865	Likely Pathogenic	Ambiguous										0.175	Likely Benign	-3.06	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.63	Benign	0.03	Affected	4.32	4	0.1817	0.5132		-2	-3	8.3	-43.03
c.2476G>A	D826N 2D AIThe SynGAP1 missense variant D826N has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on benign effects include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and Foldetta results are unavailable. Given the balance of evidence, the majority of high‑confidence predictions and the SGM consensus favor a benign outcome. Therefore, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.666105	Disordered	0.627309	Binding	0.327	0.886	0.625											-3.663	Likely Benign	0.907	Likely Pathogenic	Ambiguous										0.154	Likely Benign	-2.24	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.54	Benign	0.01	Affected			0.1520	0.8248		2	1	0.0	-0.98
c.2477A>G	D826G 2D AIThe SynGAP1 D826G missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evaluated predictors (six pathogenic vs. three benign) indicate a pathogenic impact. This prediction is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.666105	Disordered	0.627309	Binding	0.327	0.886	0.625											-6.310	Likely Benign	0.983	Likely Pathogenic	Likely Pathogenic										0.323	Likely Benign	-2.94	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.51	Benign	0.01	Affected			0.4251	0.7480		1	-1	3.1	-58.04
c.2522T>A	V841E 2D AIThe SynGAP1 missense variant V841E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM. All other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic impact. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple prediction tools and high‑accuracy methods indicates that V841E is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.622677	Disordered	0.616495	Binding	0.261	0.873	0.125											-13.750	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic										0.292	Likely Benign	-3.13	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.52	Benign	0.00	Affected			0.0939	0.1656		-2	-2	-7.7	29.98
c.2552C>G	P851R 2D AIThe SynGAP1 missense variant P851R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.526893	Binding	0.347	0.819	0.625											-4.154	Likely Benign	0.179	Likely Benign	Likely Benign										0.136	Likely Benign	-0.56	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	4.22	Benign	0.09	Tolerated			0.1252	0.3873		0	-2	-2.9	59.07
c.2575A>T	S859C 2D AIThe SynGAP1 missense variant S859C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. The high‑accuracy consensus (SGM‑Consensus) derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN reports the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. The predictions do not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.497075	Uncertain	0.288	0.819	0.375											-8.268	Likely Pathogenic	0.136	Likely Benign	Likely Benign										0.195	Likely Benign	-2.01	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	3.94	Benign	0.03	Affected			0.1046	0.6153		0	-1	3.3	16.06
c.2617A>T	S873C 2D AIThe SynGAP1 missense variant S873C is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b) predict a pathogenic impact; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a pathogenic view: AlphaMissense‑Optimized predicts benign, while the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic verdict. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence leans toward pathogenicity, and this conclusion does not contradict the ClinVar status, which currently contains no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.414856	Structured	0.649816	Binding	0.283	0.866	0.125											-8.293	Likely Pathogenic	0.502	Ambiguous	Likely Benign										0.224	Likely Benign	-2.71	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.62	Benign	0.04	Affected			0.1124	0.5887		0	-1	3.3	16.06
c.2683A>T	S895C 2D AIThe SynGAP1 missense variant S895C is reported in ClinVar as “None” and is not present in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.788093	Disordered	0.414977	Uncertain	0.294	0.925	0.750											-8.006	Likely Pathogenic	0.259	Likely Benign	Likely Benign										0.182	Likely Benign	-2.44	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.60	Benign	0.08	Tolerated			0.1072	0.6350		0	-1	3.3	16.06
c.2717T>A	L906H 2D AIThe SynGAP1 missense variant L906H is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two benign vs. two pathogenic votes) and Foldetta results are unavailable. Overall, the majority of standard predictors lean toward pathogenicity, but the most reliable high‑accuracy tool suggests a benign outcome and the consensus is unresolved. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.604312	Disordered	0.644316	Binding	0.315	0.920	0.250											-4.367	Likely Benign	0.732	Likely Pathogenic	Likely Benign										0.124	Likely Benign	-1.01	Neutral	1.000	Probably Damaging	0.997	Probably Damaging	2.18	Pathogenic	0.02	Affected			0.1125	0.1073		-2	-3	-7.0	23.98
c.2803G>A	A935T 2D AIThe SynGAP1 missense variant A935T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are not available. Overall, the majority of predictions (six benign vs. four pathogenic) lean toward a benign interpretation. Thus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.736850	Disordered	0.980490	Binding	0.286	0.865	0.625											-4.247	Likely Benign	0.228	Likely Benign	Likely Benign										0.204	Likely Benign	-1.27	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.33	Pathogenic	0.00	Affected			0.1670	0.6599		1	0	-2.5	30.03
c.2947A>T	S983C 2D AIThe SynGAP1 missense variant S983C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools cluster into two groups: benign predictions come from REVEL and AlphaMissense‑Optimized, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, whereas the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points toward a pathogenic impact. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.707965	Disordered	0.960212	Binding	0.277	0.889	0.625											-7.083	In-Between	0.741	Likely Pathogenic	Likely Benign										0.162	Likely Benign	-2.64	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.02	Pathogenic	0.00	Affected			0.1657	0.5298		0	-1	3.3	16.06
c.2953A>T	S985C 2D AIThe SynGAP1 missense variant S985C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and PROVEAN, whereas the majority of tools predict a pathogenic impact: polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify the variant as pathogenic. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is classified as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple in silico predictors indicates that S985C is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.720929	Disordered	0.941547	Binding	0.302	0.896	0.750											-8.918	Likely Pathogenic	0.860	Likely Pathogenic	Ambiguous										0.147	Likely Benign	-2.49	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.48	Pathogenic	0.00	Affected			0.1531	0.5395		0	-1	3.3	16.06
c.3022G>A	D1008N 2D AIThe SynGAP1 missense variant D1008N is listed in ClinVar (ID 1213097.0) as benign and is present in gnomAD (variant ID 6‑33443574‑G‑A). Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, a majority‑vote model of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta (combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the majority of evidence indicates a benign effect, consistent with the ClinVar classification and not contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.694846	Disordered	0.919416	Binding	0.280	0.899	0.625					Likely Benign		1	6-33443574-G-A	3	1.86e-6	-4.045	Likely Benign	0.714	Likely Pathogenic	Likely Benign										0.128	Likely Benign	-2.15	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.75	Benign	0.01	Affected	3.77	5	0.2076	0.7013		2	1	0.0	-0.98
c.3023A>G	D1008G 2D AIThe SynGAP1 D1008G missense variant (ClinVar ID 2963386.0) is listed as Uncertain in ClinVar and is present in gnomAD (ID 6‑33443575‑A‑G). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the balance of evidence leans toward a pathogenic interpretation, which does not contradict the current ClinVar designation of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.694846	Disordered	0.919416	Binding	0.280	0.899	0.625					Uncertain		1	6-33443575-A-G	1	6.20e-7	-3.213	Likely Benign	0.742	Likely Pathogenic	Likely Benign										0.203	Likely Benign	-2.84	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.65	Benign	0.01	Affected	3.77	5	0.3660	0.6073		-1	1	3.1	-58.04
c.3248A>T	K1083I 2D AIThe SynGAP1 missense variant K1083I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and the Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of a ClinVar entry, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.837511	Disordered	0.978906	Binding	0.302	0.893	1.000											-3.207	Likely Benign	0.836	Likely Pathogenic	Ambiguous										0.239	Likely Benign	-1.65	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	4.02	Benign	0.30	Tolerated			0.1394	0.3978		-2	-3	8.4	-15.01
c.3254G>C	R1085P 2D AIThe SynGAP1 missense variant R1085P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2). Foldetta results are unavailable. Overall, the majority of standard predictors (five pathogenic vs. four benign) lean toward a pathogenic interpretation, but the high‑accuracy AlphaMissense‑Optimized prediction and the inconclusive SGM Consensus temper this view. The variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.852992	Disordered	0.978838	Binding	0.270	0.888	1.000											-2.527	Likely Benign	0.759	Likely Pathogenic	Likely Benign										0.260	Likely Benign	-2.55	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.71	Benign	0.01	Affected			0.1988	0.4524		0	-2	2.9	-59.07
c.3268A>C	N1090H 2D AIThe SynGAP1 missense variant N1090H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) predict a pathogenic outcome. AlphaMissense‑Default remains uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.896620	Disordered	0.979886	Binding	0.341	0.887	1.000											-3.744	Likely Benign	0.447	Ambiguous	Likely Benign										0.094	Likely Benign	-1.42	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.67	Benign	0.10	Tolerated			0.1604	0.7550		2	1	0.3	23.04
c.3269A>T	N1090I 2D AIThe SynGAP1 missense variant N1090I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the balance of evidence from both general and high‑accuracy predictors points to a benign classification, and this conclusion does not contradict the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.896620	Disordered	0.979886	Binding	0.341	0.887	1.000											-4.356	Likely Benign	0.765	Likely Pathogenic	Likely Benign										0.173	Likely Benign	-2.14	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.67	Benign	0.02	Affected			0.0781	0.6279		-2	-3	8.0	-0.94
c.3413C>G	S1138C 2D AIThe SynGAP1 missense variant S1138C is catalogued in gnomAD (ID 6‑33444448‑C‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the preponderance of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, as no ClinVar classification exists for S1138C. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.891961	Disordered	0.738250	Binding	0.346	0.869	1.000								6-33444448-C-G	1	6.20e-7	-7.850	In-Between	0.117	Likely Benign	Likely Benign										0.425	Likely Benign	-2.48	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	5.40	Benign	0.04	Affected	4.32	4	0.1472	0.6396		-1	0	3.3	16.06
c.3455A>T	E1152V 2D AIThe SynGAP1 missense variant E1152V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.741537	Disordered	0.811118	Binding	0.395	0.846	0.500											-3.304	Likely Benign	0.978	Likely Pathogenic	Likely Pathogenic										0.408	Likely Benign	-4.65	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.33	Pathogenic	0.00	Affected			0.1247	0.6384		-2	-2	7.7	-29.98
c.3460A>C	T1154P 2D AIThe SynGAP1 missense variant T1154P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that T1154P is most likely pathogenic, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.838654	Binding	0.382	0.851	0.625											-2.513	Likely Benign	0.995	Likely Pathogenic	Likely Pathogenic										0.368	Likely Benign	-4.42	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.72	Pathogenic	0.00	Affected			0.1667	0.3732		0	-1	-0.9	-3.99
c.3461C>A	T1154K 2D AIThe SynGAP1 missense variant T1154K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Benign predictions are limited to REVEL and ESM1b. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus classifies the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that T1154K is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.838654	Binding	0.382	0.851	0.625											-3.641	Likely Benign	0.998	Likely Pathogenic	Likely Pathogenic										0.364	Likely Benign	-4.25	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.74	Pathogenic	0.00	Affected			0.1053	0.2378		0	-1	-3.2	27.07
c.3461C>T	T1154I 2D AIThe SynGAP1 missense variant T1154I is not reported in ClinVar and has no gnomAD entry. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.838654	Binding	0.382	0.851	0.625											-4.489	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.351	Likely Benign	-4.38	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.74	Pathogenic	0.00	Affected			0.0927	0.4956		0	-1	5.2	12.05
c.3464T>A	V1155E 2D AIThe SynGAP1 missense variant V1155E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments highlight a discrepancy: AlphaMissense‑Optimized predicts pathogenic, whereas the SGM‑Consensus indicates likely benign; Foldetta stability analysis is unavailable. Consequently, the evidence is evenly split between benign and pathogenic interpretations, and no ClinVar entry contradicts these findings. The variant’s clinical significance remains uncertain, with no definitive leaning toward benign or pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.750527	Disordered	0.855718	Binding	0.335	0.857	0.500											-3.175	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.204	Likely Benign	-2.01	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.58	Benign	0.02	Affected			0.0973	0.1727		-2	-2	-7.7	29.98
c.3476C>G	S1159C 2D AIThe SynGAP1 missense variant S1159C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. There is no ClinVar entry to contradict this assessment, so the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.626927	Disordered	0.867068	Binding	0.343	0.846	0.375											-6.650	Likely Benign	0.591	Likely Pathogenic	Likely Benign										0.172	Likely Benign	-1.22	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.63	Benign	0.06	Tolerated			0.0807	0.5668		0	-1	3.3	16.06
c.3554A>T	K1185I 2D AIThe SynGAP1 missense variant K1185I is listed in ClinVar with no pathogenicity classification (ClinVar status: None) and is present in the gnomAD database (gnomAD ID: 6‑33444589‑A‑T). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Based on the overall pattern of predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which remains unclassified. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.566480	Disordered	0.510264	Binding	0.642	0.638	0.625								6-33444589-A-T	1	6.20e-7	-5.101	Likely Benign	0.990	Likely Pathogenic	Likely Pathogenic										0.215	Likely Benign	-3.42	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.62	Benign	0.09	Tolerated	3.82	4	0.1154	0.3108		-3	-2	8.4	-15.01
c.3566A>T	E1189V 2D AIThe SynGAP1 E1189V missense change is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2). Foldetta stability predictions are not available. Overall, more tools (five) predict pathogenicity than benign (three), and the high‑accuracy methods do not overturn this trend. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.562014	Disordered	0.466885	Uncertain	0.704	0.623	0.625											-5.048	Likely Benign	0.950	Likely Pathogenic	Ambiguous										0.492	Likely Benign	-3.50	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	5.26	Benign	0.02	Affected			0.0467	0.4252		-2	-2	7.7	-29.98
c.3568A>T	S1190C 2D AIThe SynGAP1 missense variant S1190C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the balance of evidence favors a benign interpretation, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.575842	Disordered	0.455760	Uncertain	0.742	0.624	0.625											-6.788	Likely Benign	0.828	Likely Pathogenic	Ambiguous										0.418	Likely Benign	-1.93	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	5.22	Benign	0.07	Tolerated			0.1144	0.4294		0	-1	3.3	16.06
c.3580A>T	R1194W 2D AIThe SynGAP1 missense variant R1194W is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: benign predictions are limited to FATHMM, whereas the remaining methods—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) confirms a likely pathogenic status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence points to the variant being most likely pathogenic, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.685117	Disordered	0.425297	Uncertain	0.796	0.602	0.375											-9.583	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.514	Likely Pathogenic	-2.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	5.41	Benign	0.00	Affected			0.1252	0.3162		2	-3	3.6	30.03
c.3581G>T	R1194M 2D AIThe SynGAP1 missense variant R1194M is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM‑Consensus remains benign; Foldetta results are unavailable. Overall, the majority of high‑confidence tools and the consensus prediction lean toward a benign classification. Thus, the variant is most likely benign, and this assessment does not contradict ClinVar status, which currently has no entry for R1194M. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.685117	Disordered	0.425297	Uncertain	0.796	0.602	0.375											-6.362	Likely Benign	0.981	Likely Pathogenic	Likely Pathogenic										0.381	Likely Benign	-2.13	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	5.42	Benign	0.01	Affected			0.1471	0.3165		0	-1	6.4	-24.99
c.3622C>G	R1208G 2D AIThe SynGAP1 missense variant R1208G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as likely pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.604312	Disordered	0.566942	Binding	0.899	0.569	0.375											-12.261	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.198	Likely Benign	-4.66	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.50	Benign	0.01	Affected			0.3287	0.2847		-3	-2	4.1	-99.14
c.3623G>T	R1208L 2D AIThe SynGAP1 missense variant R1208L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence indicates that R1208L is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.604312	Disordered	0.566942	Binding	0.899	0.569	0.375											-10.576	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.204	Likely Benign	-4.70	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.51	Benign	0.01	Affected			0.1621	0.3816		-3	-2	8.3	-43.03
c.3718C>G	R1240G 2D AIThe SynGAP1 missense variant R1240G is not reported in ClinVar and has no entry in gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus agrees. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the preponderance of evidence indicates that R1240G is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.541878	Disordered	0.511333	Binding	0.865	0.540	0.375											-9.763	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic										0.280	Likely Benign	-5.48	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.67	Pathogenic	0.00	Affected			0.3102	0.2895		-3	-2	4.1	-99.14
c.3719G>T	R1240L 2D AIThe SynGAP1 missense variant R1240L is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. No Foldetta stability analysis is available for this variant. Based on the preponderance of pathogenic predictions, R1240L is most likely pathogenic, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.541878	Disordered	0.511333	Binding	0.865	0.540	0.375											-10.181	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic										0.372	Likely Benign	-5.48	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.67	Pathogenic	0.00	Affected			0.1513	0.3394		-3	-2	8.3	-43.03
c.3766G>A	D1256N 2D AIThe SynGAP1 D1256N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.549308	Disordered	0.445789	Uncertain	0.876	0.571	0.625											-10.375	Likely Pathogenic	0.897	Likely Pathogenic	Ambiguous										0.290	Likely Benign	-3.85	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.67	Pathogenic	0.00	Affected			0.0832	0.4219		2	1	0.0	-0.98
c.3767A>G	D1256G 2D AIThe SynGAP1 missense variant D1256G is not reported in ClinVar and has no entry in gnomAD. Prediction tools that assess the variant’s effect fall into two groups: the benign‑predicting REVEL score, and a consensus of pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates likely pathogenicity. Foldetta results are unavailable. Overall, the preponderance of evidence from both general and high‑accuracy tools points to a pathogenic effect for D1256G. This conclusion is consistent with the absence of ClinVar annotation, so there is no contradiction with existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.549308	Disordered	0.445789	Uncertain	0.876	0.571	0.625											-11.341	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.457	Likely Benign	-5.45	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.65	Pathogenic	0.00	Affected			0.2886	0.5040		1	-1	3.1	-58.04
c.3805G>A	V1269M 2D AIThe SynGAP1 missense variant V1269M is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (majority vote) is pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect for V1269M, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.433034	Structured	0.787464	Binding	0.843	0.647	0.125											-3.743	Likely Benign	0.977	Likely Pathogenic	Likely Pathogenic										0.300	Likely Benign	-2.53	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.08	Pathogenic	0.00	Affected			0.0582	0.3676		2	1	-2.3	32.06
c.3821G>C	R1274P 2D AIThe SynGAP1 missense variant R1274P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic effect: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence indicates that R1274P is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.613573	Disordered	0.779985	Binding	0.746	0.688	0.625											-6.145	Likely Benign	0.955	Likely Pathogenic	Ambiguous										0.179	Likely Benign	-4.02	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.48	Pathogenic	0.01	Affected			0.2166	0.3095		0	-2	2.9	-59.07
c.3880G>C	A1294P 2D AIThe SynGAP1 missense variant A1294P is catalogued in gnomAD (6‑33447928‑G‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—yields a 2‑to‑2 split and is therefore inconclusive; Foldetta results are not available. Overall, the balance of evidence leans toward a pathogenic effect, though the single high‑accuracy benign call and the inconclusive consensus temper certainty. This assessment does not conflict with ClinVar, which currently contains no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.784345	Disordered	0.895011	Binding	0.565	0.806	0.625								6-33447928-G-C	1	6.45e-7	-2.688	Likely Benign	0.220	Likely Benign	Likely Benign										0.367	Likely Benign	-3.79	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	2.14	Pathogenic	0.00	Affected	3.77	5	0.1682	0.3207		-1	1	-3.4	26.04
c.4003G>A	G1335S 2D AIThe SynGAP1 missense variant G1335S is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33451877‑G‑A). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict a pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that G1335S is most likely pathogenic, which is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.891961	Disordered	0.967705	Binding	0.323	0.724	0.750					Conflicting		2	6-33451877-G-A	3	2.37e-6	-4.495	Likely Benign	0.986	Likely Pathogenic	Likely Pathogenic										0.362	Likely Benign	-3.79	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	2.04	Pathogenic	0.00	Affected	3.77	5	0.2452	0.5895		1	0	-0.4	30.03
c.443C>A	P148H 2D AIThe SynGAP1 missense variant P148H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect for P148H, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.500109	Binding	0.372	0.837	0.625											-11.034	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic										0.169	Likely Benign	-3.21	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.90	Benign	0.00	Affected			0.1881	0.3847		0	-2	-1.6	40.02
c.749T>G	V250G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V250G missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools largely agree on a deleterious effect: pathogenic calls come from REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (both HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default, while only FATHMM predicts a benign outcome. Uncertain results are reported by FoldX and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, AlphaMissense‑Optimized remains uncertain, and Foldetta is pathogenic. Taken together, the overwhelming majority of evidence indicates a pathogenic effect. This conclusion is consistent with the absence of a ClinVar classification; there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.447574	Structured	0.244075	Uncertain	0.778	0.324	0.125											-11.255	Likely Pathogenic	0.917	Likely Pathogenic	Ambiguous	1.65	Ambiguous	0.3	3.18	Destabilizing	2.42	Destabilizing	2.08	Destabilizing	0.900	Likely Pathogenic	-5.90	Deleterious	0.879	Possibly Damaging	0.997	Probably Damaging	5.75	Benign	0.00	Affected			0.1884	0.1996		-1	-3	-4.6	-42.08
c.763G>C	D255H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D255H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from premPS and FATHMM, while pathogenic predictions are made by SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results are reported by FoldX, Rosetta, and Foldetta. High‑accuracy methods reinforce the pathogenic interpretation: AlphaMissense‑Optimized predicts Pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, remains Uncertain. Overall, the consensus of the available predictions points to a pathogenic effect for D255H, and this conclusion is consistent with the lack of ClinVar annotation (no contradiction). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.501700	Disordered	0.219132	Uncertain	0.801	0.273	0.250											-14.645	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.72	Ambiguous	0.2	1.17	Ambiguous	1.45	Ambiguous	0.44	Likely Benign	0.808	Likely Pathogenic	-5.93	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	5.76	Benign	0.00	Affected			0.1447	0.5211		1	-1	0.3	22.05
c.763G>T	D255Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D255Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include premPS and FATHMM, while the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Predictions from FoldX, Rosetta, and Foldetta are uncertain and therefore not used as evidence. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta as Uncertain. Based on the overall consensus of the available predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.501700	Disordered	0.219132	Uncertain	0.801	0.273	0.250											-13.180	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	1.25	Ambiguous	0.2	0.96	Ambiguous	1.11	Ambiguous	0.13	Likely Benign	0.832	Likely Pathogenic	-7.77	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	5.73	Benign	0.00	Affected			0.0464	0.5178		-4	-3	2.2	48.09
c.781G>C	D261H 2D AIThe SynGAP1 missense variant D261H is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect are premPS and FATHMM, while the remaining tools—SGM‑Consensus, REVEL, FoldX, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact; Rosetta is uncertain and is treated as unavailable. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic (3 pathogenic vs. 1 benign); and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. Thus, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.284882	Structured	0.422514	Uncertain	0.883	0.264	0.125											-13.688	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic	4.33	Destabilizing	3.2	0.93	Ambiguous	2.63	Destabilizing	0.33	Likely Benign	0.780	Likely Pathogenic	-3.67	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	6.04	Benign	0.01	Affected			0.0937	0.5465		1	-1	0.3	22.05
c.781G>T	D261Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D261Y missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are premPS and FATHMM, while the remaining tools—SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect; and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. No prediction or folding stability result is missing or inconclusive beyond the stated uncertainties. Overall, the preponderance of evidence points to a pathogenic effect for D261Y, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.284882	Structured	0.422514	Uncertain	0.883	0.264	0.125											-14.961	Likely Pathogenic	0.955	Likely Pathogenic	Ambiguous	2.93	Destabilizing	2.1	0.81	Ambiguous	1.87	Ambiguous	-0.12	Likely Benign	0.886	Likely Pathogenic	-5.50	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	5.73	Benign	0.01	Affected			0.0474	0.5476		-4	-3	2.2	48.09
c.811G>A	A271T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A271T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining evidence—premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—consistently predict pathogenicity. FoldX, Rosetta, and Foldetta are inconclusive, and AlphaMissense‑Optimized also yields an uncertain result. High‑accuracy assessments show that the SGM‑Consensus (majority vote) predicts pathogenicity, while AlphaMissense‑Optimized and Foldetta remain unavailable. Taken together, the overwhelming majority of reliable predictors classify the variant as pathogenic, and this conclusion does not conflict with the ClinVar status, which currently has no entry for A271T. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.125101	Structured	0.413873	Uncertain	0.939	0.220	0.125											-9.564	Likely Pathogenic	0.934	Likely Pathogenic	Ambiguous	0.59	Ambiguous	0.1	0.54	Ambiguous	0.57	Ambiguous	1.00	Destabilizing	0.498	Likely Benign	-3.68	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	0.66	Pathogenic	0.01	Affected			0.1076	0.4691		1	0	-2.5	30.03
c.814C>G	R272G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R272G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions are limited to REVEL, whereas pathogenic predictions are made by FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain results come from Rosetta and AlphaMissense‑Optimized. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a destabilizing, pathogenic effect. Overall, the preponderance of evidence indicates the variant is most likely pathogenic, and this assessment is consistent with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.071867	Structured	0.425620	Uncertain	0.925	0.215	0.125											-11.540	Likely Pathogenic	0.831	Likely Pathogenic	Ambiguous	3.40	Destabilizing	0.0	1.94	Ambiguous	2.67	Destabilizing	1.06	Destabilizing	0.479	Likely Benign	-4.57	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.75	Pathogenic	0.01	Affected			0.3082	0.3062		-3	-2	4.1	-99.14
c.815G>T	R272L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R272L missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, and premPS. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain or inconclusive results come from FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, while AlphaMissense‑Optimized and Foldetta remain uncertain. Overall, the majority of evaluated tools predict a pathogenic impact. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.071867	Structured	0.425620	Uncertain	0.925	0.215	0.125											-10.796	Likely Pathogenic	0.796	Likely Pathogenic	Ambiguous	1.66	Ambiguous	0.3	-0.46	Likely Benign	0.60	Ambiguous	0.41	Likely Benign	0.470	Likely Benign	-4.57	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.75	Pathogenic	0.01	Affected			0.1691	0.4230		-3	-2	8.3	-43.03
c.835C>G	R279G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R279G is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated tools predict a pathogenic impact: FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote) which labels it “Likely Pathogenic.” AlphaMissense‑Optimized is uncertain, providing no definitive evidence. High‑accuracy assessments further support pathogenicity: the SGM‑Consensus remains “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a destabilizing, pathogenic effect. Based on the overwhelming majority of predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.155435	Structured	0.309382	Uncertain	0.887	0.257	0.125											-9.941	Likely Pathogenic	0.920	Likely Pathogenic	Ambiguous	3.10	Destabilizing	0.7	2.85	Destabilizing	2.98	Destabilizing	1.11	Destabilizing	0.442	Likely Benign	-5.37	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.92	Pathogenic	0.02	Affected			0.2961	0.2209		-3	-2	4.1	-99.14
c.836G>T	R279L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R279L is reported in gnomAD (ID 6‑33437741‑G‑T) but has no ClinVar entry. Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, and premPS. Those that predict a pathogenic effect comprise SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a unanimous majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evidence points to a pathogenic impact. This conclusion is not contradicted by ClinVar, which contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.155435	Structured	0.309382	Uncertain	0.887	0.257	0.125								6-33437741-G-T	1	6.20e-7	-12.390	Likely Pathogenic	0.926	Likely Pathogenic	Ambiguous	0.01	Likely Benign	0.2	0.14	Likely Benign	0.08	Likely Benign	0.39	Likely Benign	0.576	Likely Pathogenic	-5.37	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.91	Pathogenic	0.03	Affected	3.39	18	0.1682	0.3266		-2	-3	8.3	-43.03
c.859G>A	D287N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D287N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions (REVEL, FoldX, premPS, SIFT) and pathogenic predictions (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default). Two tools give uncertain results (Rosetta, AlphaMissense‑Optimized). High‑accuracy assessments further separate the evidence: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic effect; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign impact. Overall, the majority of conventional predictors lean toward pathogenicity, while the most accurate stability‑based method suggests benign. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.102787	Structured	0.389029	Uncertain	0.912	0.268	0.000											-10.167	Likely Pathogenic	0.944	Likely Pathogenic	Ambiguous	0.16	Likely Benign	0.3	-0.54	Ambiguous	-0.19	Likely Benign	0.05	Likely Benign	0.372	Likely Benign	-4.60	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.62	Pathogenic	0.06	Tolerated			0.1338	0.8194		2	1	0.0	-0.98
c.860A>G	D287G 2D AIThe SynGAP1 missense variant D287G is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include Foldetta, premPS, and Rosetta, whereas the majority of other in silico predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict it to be pathogenic; FoldX is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the preponderance of predictions indicates a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.102787	Structured	0.389029	Uncertain	0.912	0.268	0.000											-13.558	Likely Pathogenic	0.967	Likely Pathogenic	Likely Pathogenic	0.61	Ambiguous	1.1	0.31	Likely Benign	0.46	Likely Benign	0.38	Likely Benign	0.521	Likely Pathogenic	-6.43	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.59	Pathogenic	0.01	Affected			0.4688	0.7390		1	-1	3.1	-58.04
c.862G>A	D288N 2D 3DClick to see structure in 3D Viewer AISynGAP1 D288N is listed in ClinVar with an uncertain significance (ClinVar ID 2572204.0) and is present in gnomAD (6‑33437767‑G‑A). Computational predictors are divided: benign calls come from REVEL, FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized, while pathogenic calls come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic. Because the majority of high‑accuracy tools predict benign and the overall split of predictions is even, the variant is most likely benign, which does not contradict the ClinVar status of uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.125101	Structured	0.395525	Uncertain	0.873	0.261	0.000					Uncertain		1	6-33437767-G-A	2	1.24e-6	-10.535	Likely Pathogenic	0.521	Ambiguous	Likely Benign	-0.39	Likely Benign	0.1	0.01	Likely Benign	-0.19	Likely Benign	-0.03	Likely Benign	0.321	Likely Benign	-3.73	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.78	Pathogenic	0.05	Affected	3.38	23	0.1398	0.5770		1	2	0.0	-0.98
c.863A>G	D288G 2D 3DClick to see structure in 3D Viewer AISynGAP1 D288G is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, Rosetta, premPS, SIFT, AlphaMissense‑Optimized, and Foldetta. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. No folding‑stability result is available from FoldX. Overall, the balance of evidence slightly favors a pathogenic interpretation, with one high‑accuracy tool supporting benignity. The prediction does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.125101	Structured	0.395525	Uncertain	0.873	0.261	0.000											-8.531	Likely Pathogenic	0.739	Likely Pathogenic	Likely Benign	-0.71	Ambiguous	0.4	0.21	Likely Benign	-0.25	Likely Benign	-0.15	Likely Benign	0.436	Likely Benign	-5.03	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.05	Pathogenic	0.13	Tolerated			0.4126	0.5934		1	-1	3.1	-58.04
c.874G>A	A292T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A292T is not reported in ClinVar and is absent from gnomAD. Prediction tools largely converge on a deleterious effect: only REVEL classifies it as benign, whereas FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (both HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized returns a pathogenic score, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labels it Likely Pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts a destabilizing, pathogenic effect. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.247041	Structured	0.362042	Uncertain	0.929	0.256	0.000											-11.039	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	2.16	Destabilizing	0.7	3.42	Destabilizing	2.79	Destabilizing	1.08	Destabilizing	0.457	Likely Benign	-3.68	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.68	Pathogenic	0.01	Affected			0.1691	0.7377		1	0	-2.5	30.03
c.877C>A	R293S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R293S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a deleterious effect include REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Tools that are inconclusive or uncertain are Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, the SGM‑Consensus indicating a likely pathogenic outcome, while Foldetta’s stability analysis remains uncertain. Taken together, the overwhelming majority of evidence points to a pathogenic impact for R293S. This conclusion is consistent with the lack of ClinVar annotation, as there is no conflicting status to contradict the prediction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.335645	Structured	0.338192	Uncertain	0.924	0.269	0.125											-14.103	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.66	Destabilizing	0.2	1.30	Ambiguous	1.98	Ambiguous	0.71	Ambiguous	0.561	Likely Pathogenic	-5.52	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.51	Pathogenic	0.01	Affected			0.2794	0.5045		0	-1	3.7	-69.11
c.877C>G	R293G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R293G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic, while premPS remains uncertain. High‑accuracy assessments corroborate this trend: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports a likely pathogenic outcome, and Foldetta (integrating FoldX‑MD and Rosetta stability outputs) also indicates pathogenicity. No tool suggests a benign effect. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.335645	Structured	0.338192	Uncertain	0.924	0.269	0.125											-15.861	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.70	Destabilizing	0.2	2.35	Destabilizing	3.03	Destabilizing	0.57	Ambiguous	0.604	Likely Pathogenic	-6.43	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.45	Pathogenic	0.02	Affected			0.3235	0.3738		-3	-2	4.1	-99.14
c.878G>T	R293L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R293L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions are made by REVEL and premPS, while the remaining evaluated tools (SIFT, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all predict pathogenicity. Uncertain results from FoldX, Rosetta, and Foldetta are treated as unavailable. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta provides no definitive stability change. Consequently, the variant is most likely pathogenic based on the consensus of predictive tools, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.335645	Structured	0.338192	Uncertain	0.924	0.269	0.125											-15.502	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	1.56	Ambiguous	0.2	0.93	Ambiguous	1.25	Ambiguous	0.08	Likely Benign	0.493	Likely Benign	-6.43	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.46	Pathogenic	0.01	Affected			0.1815	0.4987		-3	-2	8.3	-43.03
c.895C>A	R299S 2D 3DClick to see structure in 3D Viewer AISynGAP1 R299S is not reported in ClinVar and is absent from gnomAD. Among in‑silico predictors, benign calls come from REVEL and SIFT, while pathogenic calls are made by FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. Uncertain results are reported by Rosetta, ESM1b, and AlphaMissense‑Optimized. High‑accuracy methods give a pathogenic verdict: AlphaMissense‑Optimized is inconclusive, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) also predicts pathogenic. Overall, the evidence points to a pathogenic effect, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.262979	Uncertain	0.819	0.295	0.500											-7.276	In-Between	0.882	Likely Pathogenic	Ambiguous	2.86	Destabilizing	0.3	1.46	Ambiguous	2.16	Destabilizing	1.07	Destabilizing	0.241	Likely Benign	-3.20	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.75	Pathogenic	0.07	Tolerated			0.2780	0.5057		0	-1	3.7	-69.11
c.895C>G	R299G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R299G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and AlphaMissense‑Optimized, whereas the remaining 13 tools (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) all predict pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized indicates a benign change, but the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta outputs) both predict pathogenicity. With the majority of evidence pointing to a damaging effect, the variant is most likely pathogenic. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.262979	Uncertain	0.819	0.295	0.500											-8.354	Likely Pathogenic	0.629	Likely Pathogenic	Likely Benign	3.58	Destabilizing	0.2	3.16	Destabilizing	3.37	Destabilizing	1.37	Destabilizing	0.248	Likely Benign	-3.84	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.79	Pathogenic	0.02	Affected			0.3361	0.4150		-3	-2	4.1	-99.14
c.896G>T	R299L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R299L is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, ESM1b, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. Stability‑based methods FoldX, Rosetta, Foldetta, and premPS returned uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the majority of consensus predictions favor a pathogenic effect, and the high‑accuracy tools do not overturn this trend. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists for R299L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.262979	Uncertain	0.819	0.295	0.500											-5.171	Likely Benign	0.645	Likely Pathogenic	Likely Benign	1.37	Ambiguous	0.6	0.77	Ambiguous	1.07	Ambiguous	0.59	Ambiguous	0.356	Likely Benign	-4.03	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.65	Pathogenic	0.02	Affected			0.2027	0.5202		-3	-2	8.3	-43.03
c.910G>A	D304N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant D304N is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of evidence points to a benign impact, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.352862	Structured	0.285053	Uncertain	0.764	0.271	0.250					Uncertain		1				-6.194	Likely Benign	0.391	Ambiguous	Likely Benign	0.30	Likely Benign	0.1	-0.08	Likely Benign	0.11	Likely Benign	0.21	Likely Benign	0.345	Likely Benign	-4.18	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.81	Pathogenic	0.03	Affected	3.38	23	0.1353	0.7205		1	2	0.0	-0.98
c.911A>G	D304G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D304G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, ESM1b, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default, FoldX, Rosetta, and Foldetta are uncertain and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicting pathogenic, and Foldetta remaining uncertain. Overall, the majority of tools (five pathogenic vs. four benign) and the SGM Consensus support a pathogenic classification. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.352862	Structured	0.285053	Uncertain	0.764	0.271	0.250											-2.713	Likely Benign	0.546	Ambiguous	Likely Benign	1.02	Ambiguous	0.2	0.95	Ambiguous	0.99	Ambiguous	0.47	Likely Benign	0.380	Likely Benign	-5.32	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.75	Pathogenic	0.02	Affected			0.4590	0.6451		1	-1	3.1	-58.04
c.961C>A	R321S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R321S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, premPS, PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Two tools—FoldX and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of predictions lean toward a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.175930	Structured	0.423273	Uncertain	0.931	0.297	0.125											-10.146	Likely Pathogenic	0.497	Ambiguous	Likely Benign	0.66	Ambiguous	0.1	-0.30	Likely Benign	0.18	Likely Benign	0.24	Likely Benign	0.379	Likely Benign	-2.27	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.00	Pathogenic	0.10	Tolerated			0.2958	0.2785		0	-1	3.7	-69.11
c.961C>G	R321G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R321G is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, Rosetta, AlphaMissense‑Default, AlphaMissense‑Optimized, and premPS. Tools that predict a pathogenic effect comprise SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of conventional predictors lean toward pathogenicity, while the high‑accuracy subset is mixed, with one benign, one pathogenic, and one uncertain result. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.175930	Structured	0.423273	Uncertain	0.931	0.297	0.125											-10.554	Likely Pathogenic	0.293	Likely Benign	Likely Benign	0.90	Ambiguous	0.1	0.28	Likely Benign	0.59	Ambiguous	0.49	Likely Benign	0.430	Likely Benign	-3.70	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.92	Pathogenic	0.04	Affected			0.3224	0.2898		-3	-2	4.1	-99.14
c.962G>T	R321L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R321L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Foldetta, premPS, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include SIFT, polyPhen‑2 (HumDiv and HumVar), PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign; FoldX and Rosetta individually are inconclusive. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.175930	Structured	0.423273	Uncertain	0.931	0.297	0.125											-11.709	Likely Pathogenic	0.551	Ambiguous	Likely Benign	0.54	Ambiguous	0.0	-0.58	Ambiguous	-0.02	Likely Benign	0.18	Likely Benign	0.451	Likely Benign	-4.06	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.93	Pathogenic	0.03	Affected			0.1745	0.4048		-3	-2	8.3	-43.03
c.970C>G	R324G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R324G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default; the SGM‑Consensus score is “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. With the majority of evidence pointing to deleterious impact and two of the three high‑accuracy methods supporting pathogenicity, the variant is most likely pathogenic. This conclusion does not contradict any ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.257454	Structured	0.426893	Uncertain	0.954	0.397	0.000											-12.266	Likely Pathogenic	0.708	Likely Pathogenic	Likely Benign	2.99	Destabilizing	0.1	3.18	Destabilizing	3.09	Destabilizing	1.27	Destabilizing	0.496	Likely Benign	-2.64	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.84	Pathogenic	0.39	Tolerated			0.3546	0.4135		-3	-2	4.1	-99.14
c.971G>T	R324L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R324L is catalogued in gnomAD (6-33437876‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, and SIFT; pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts a benign effect, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic outcome, and Foldetta (integrating FoldX‑MD and Rosetta outputs) reports a benign stability change. Overall, the majority of evidence points toward a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.257454	Structured	0.426893	Uncertain	0.954	0.397	0.000								6-33437876-G-T	1	6.20e-7	-10.328	Likely Pathogenic	0.575	Likely Pathogenic	Likely Benign	-0.28	Likely Benign	0.0	-0.08	Likely Benign	-0.18	Likely Benign	0.29	Likely Benign	0.489	Likely Benign	-2.20	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	1.86	Pathogenic	0.63	Tolerated	3.39	22	0.2310	0.5607		-2	-3	8.3	-43.03
c.994G>A	D332N 2D 3DClick to see structure in 3D Viewer AISynGAP1 D332N is not reported in ClinVar and is absent from gnomAD. Benign predictions come from REVEL, Rosetta, premPS, and SIFT, while pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default; SGM‑Consensus indicates a likely pathogenic outcome. FoldX and Foldetta give uncertain results. High‑accuracy tools show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as uncertain. Overall, the majority of conventional predictors lean toward pathogenicity, but the high‑accuracy AlphaMissense‑Optimized result is benign and Foldetta is inconclusive. Thus, the variant is most likely pathogenic based on the collective evidence, and this assessment does not contradict ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.339168	Structured	0.336528	Uncertain	0.537	0.445	0.375											-10.931	Likely Pathogenic	0.771	Likely Pathogenic	Likely Benign	1.20	Ambiguous	0.1	-0.16	Likely Benign	0.52	Ambiguous	0.49	Likely Benign	0.396	Likely Benign	-4.14	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.32	Pathogenic	0.11	Tolerated			0.0785	0.3963		2	1	0.0	-0.98
c.995A>G	D332G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D332G missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only SIFT, whereas the majority of tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) predict a pathogenic impact. Predictions that are inconclusive or uncertain are given by FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for D332G, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.339168	Structured	0.336528	Uncertain	0.537	0.445	0.375											-10.844	Likely Pathogenic	0.860	Likely Pathogenic	Ambiguous	1.78	Ambiguous	0.3	0.69	Ambiguous	1.24	Ambiguous	0.63	Ambiguous	0.539	Likely Pathogenic	-5.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.31	Pathogenic	0.07	Tolerated			0.3052	0.4765		1	-1	3.1	-58.04
c.1000A>C	K334Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K334Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, Foldetta, and premPS. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. With seven tools favoring pathogenicity versus five favoring benign, the overall prediction leans toward pathogenic. This conclusion does not contradict ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.377384	Structured	0.325972	Uncertain	0.544	0.414	0.500											-8.185	Likely Pathogenic	0.810	Likely Pathogenic	Ambiguous	0.08	Likely Benign	0.0	0.10	Likely Benign	0.09	Likely Benign	0.46	Likely Benign	0.357	Likely Benign	-3.67	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.74	Pathogenic	0.03	Affected			0.4519	0.1062		1	1	0.4	-0.04
c.1001A>C	K334T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K334T is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, and premPS. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Predictions that are inconclusive or uncertain are FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts a likely pathogenic outcome, AlphaMissense‑Optimized is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also uncertain. Overall, the majority of evidence points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.377384	Structured	0.325972	Uncertain	0.544	0.414	0.500											-8.313	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	0.78	Ambiguous	0.3	0.21	Likely Benign	0.50	Ambiguous	0.17	Likely Benign	0.320	Likely Benign	-5.51	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.78	Pathogenic	0.02	Affected			0.2062	0.2978		0	-1	3.2	-27.07
c.1002G>C	K334N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K334N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and premPS. Tools that predict a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus score, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic.” Separately, the high‑accuracy AlphaMissense‑Optimized tool predicts pathogenicity, the SGM‑Consensus also predicts pathogenicity, while the Foldetta stability assessment predicts a benign effect. Overall, the majority of predictions (8 pathogenic vs. 5 benign) and the high‑accuracy consensus suggest that K334N is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.377384	Structured	0.325972	Uncertain	0.544	0.414	0.500											-9.581	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	0.15	Likely Benign	0.1	-0.25	Likely Benign	-0.05	Likely Benign	0.18	Likely Benign	0.249	Likely Benign	-4.59	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.77	Pathogenic	0.02	Affected			0.3716	0.0958		1	0	0.4	-14.07
c.1002G>T	K334N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K334N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and premPS. Tools that predict a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus score, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic.” Separately, the high‑accuracy AlphaMissense‑Optimized tool predicts pathogenicity, the SGM‑Consensus also predicts pathogenicity, while the Foldetta stability assessment predicts a benign effect. Overall, the majority of predictions (8 pathogenic vs. 5 benign) and the high‑accuracy consensus suggest that K334N is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.377384	Structured	0.325972	Uncertain	0.544	0.414	0.500											-9.581	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	0.15	Likely Benign	0.1	-0.25	Likely Benign	-0.05	Likely Benign	0.18	Likely Benign	0.249	Likely Benign	-4.59	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.77	Pathogenic	0.02	Affected			0.3716	0.0958		1	0	0.4	-14.07
c.1003C>T	R335C 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R335C is listed in ClinVar with an uncertain significance (ClinVar ID 2835865.0) and is present in gnomAD (ID 6‑33437908‑C‑T). Functional prediction tools cluster into two groups: benign predictions come from REVEL and premPS, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Predictions that are inconclusive are AlphaMissense‑Optimized, FoldX, Rosetta, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic effect. This conclusion aligns with the ClinVar designation of uncertain significance, which does not contradict the prediction that the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.305330	Structured	0.331028	Uncertain	0.483	0.428	0.500					Uncertain		1	6-33437908-C-T	1	6.20e-7	-14.354	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	0.53	Ambiguous	0.1	0.85	Ambiguous	0.69	Ambiguous	0.46	Likely Benign	0.277	Likely Benign	-5.69	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.67	Pathogenic	0.01	Affected	3.38	22	0.2882	0.3290		-3	-4	7.0	-53.05
c.1004G>A	R335H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R335H is listed in ClinVar with an uncertain significance and is present in gnomAD (variant ID 6-33437909‑G‑A). Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, and Foldetta, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain results are reported by FoldX, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as pathogenic, whereas Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the preponderance of evidence points to a pathogenic impact, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.305330	Structured	0.331028	Uncertain	0.483	0.428	0.500					Uncertain		1	6-33437909-G-A	2	1.24e-6	-12.521	Likely Pathogenic	0.831	Likely Pathogenic	Ambiguous	0.58	Ambiguous	0.1	0.22	Likely Benign	0.40	Likely Benign	0.72	Ambiguous	0.132	Likely Benign	-3.02	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.70	Pathogenic	0.03	Affected	3.38	22	0.2316	0.2330		2	0	1.3	-19.05	242.4	82.1	-2.4	0.6	-0.1	0.1								Uncertain	The guanidinium group of Arg335, located in a β hairpin loop linking two anti-parallel β sheet strands (res. Ala322-Asp330, res. Gly341-Pro349), faces the post-synaptic inner membrane surface. In the WT simulations, the Arg335 side chain dynamically forms salt bridges with the carboxylate groups of Asp322, Asp338, and Asp616. In contrast, the imidazole ring of His335, which is not double protonated and thus not positively charged in the variant simulations, continues to move dynamically without forming any lasting or strong interactions. Importantly, the positively charged arginine residues of the C2 domain are ideal membrane anchors for ensuring SynGAP-membrane association. However, this phenomenon cannot be addressed using solvent-only simulations.
c.1010A>T	K337M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K337M missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that classify it as benign include REVEL, FoldX, premPS, and the protein‑folding stability method Foldetta. In contrast, the majority of in‑silico predictors flag it as pathogenic: SIFT, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Pathogenic” verdict. For high‑accuracy assessment, AlphaMissense‑Optimized remains pathogenic, the SGM‑Consensus also indicates likely pathogenic, whereas Foldetta predicts benign stability. No prediction is inconclusive; Rosetta is uncertain but not counted as evidence. Overall, the preponderance of evidence points to a pathogenic effect, and this assessment does not contradict any ClinVar classification because none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.348540	Uncertain	0.449	0.438	0.500											-13.406	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.28	Likely Benign	0.1	0.61	Ambiguous	0.45	Likely Benign	-0.24	Likely Benign	0.345	Likely Benign	-5.32	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.66	Pathogenic	0.00	Affected			0.0862	0.3871		0	-1	5.8	3.02
c.1025A>C	Y342S 2D 3DClick to see structure in 3D Viewer AISynGAP1 variant Y342S is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of algorithms predict a pathogenic impact: FoldX, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and the Foldetta stability assessment (combining FoldX‑MD and Rosetta). Uncertain results come from premPS, ESM1b, and AlphaMissense‑Optimized. High‑accuracy methods specifically give AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta as pathogenic. Overall, the preponderance of evidence points to a pathogenic effect, which contradicts the ClinVar uncertain classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.366687	Structured	0.408200	Uncertain	0.866	0.487	0.250					Uncertain		2				-7.996	In-Between	0.925	Likely Pathogenic	Ambiguous	3.03	Destabilizing	0.1	2.87	Destabilizing	2.95	Destabilizing	0.93	Ambiguous	0.407	Likely Benign	-6.60	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.75	Pathogenic	0.04	Affected	3.37	25	0.4617	0.2637		-3	-2	0.5	-76.10	200.1	77.8	0.0	0.0	-0.2	0.1								Potentially Pathogenic	The phenol ring of Tyr342, located at the end of an anti-parallel β sheet strand (res. Gly341-Pro349), faces outward in the C2 domain. In the WT simulations, the phenol ring of Tyr342 contributes to a triple tyrosine stack (Tyr342, Tyr328, and Tyr281) that links together three anti-parallel β sheet strands. Additionally, it shields Gly344 from the solvent, reducing its exposure and providing stability for the β-sandwich. This motif also contributes to a twist formation in the β sheet.In the variant simulations, the Ser342 side chain cannot participate in the stack formation. Instead, the hydroxyl group of the Ser342 side chain forms a hydrogen bond with the imidazole ring of His326 in a neighboring β strand (res. Ala322-Asp330). This disrupts the formation of a hydrogen bond between His326 and the carboxylate group of the Glu283 side chain from another β strand (res. Arg279-Cys285). Although these changes in surface interactions could weaken the characteristic twist that strengthens the β sheet fold, no major structural effects are observed in the variant simulations. The residue swap could also affect the SynGAP-membrane association, as the hydroxyl group of Ser342 could form hydrogen bonds with membrane-facing loop residues. However, this phenomenon cannot be addressed using solvent-only simulations.
c.1091C>A	P364H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P364H is reported in gnomAD (ID 6‑33437996‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support this dichotomy: AlphaMissense‑Optimized classifies the variant as benign, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels it pathogenic. The protein‑folding stability predictor Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not conflict with ClinVar status, which currently lacks an entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.390993	Structured	0.439474	Uncertain	0.942	0.590	0.250								6-33437996-C-A			-10.744	Likely Pathogenic	0.632	Likely Pathogenic	Likely Benign	1.65	Ambiguous	0.9	0.25	Likely Benign	0.95	Ambiguous	0.77	Ambiguous	0.407	Likely Benign	-6.96	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.55	Pathogenic	0.02	Affected	3.39	20	0.1800	0.4584		-2	0	-1.6	40.02
c.1126G>A	G376S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G376S is reported in gnomAD (ID 6‑33438031‑G‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Pathogenic predictions arise from FoldX, polyPhen‑2 (HumDiv and HumVar), and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates benign, while Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain. Overall, the majority of evidence points to a benign effect; this conclusion is not contradicted by ClinVar, which contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.680603	Disordered	0.428979	Uncertain	0.326	0.869	0.625								6-33438031-G-A	1	6.21e-7	-4.913	Likely Benign	0.087	Likely Benign	Likely Benign	2.30	Destabilizing	0.5	-0.45	Likely Benign	0.93	Ambiguous	0.32	Likely Benign	0.471	Likely Benign	-0.73	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	1.33	Pathogenic	0.22	Tolerated	4.32	12	0.2831	0.4801		0	1	-0.4	30.03
c.1127G>A	G376D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G376D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. The remaining tools—Rosetta, Foldetta, premPS, and ESM1b—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicting pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) yielding an uncertain stability change. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict the ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.680603	Disordered	0.428979	Uncertain	0.326	0.869	0.625											-7.125	In-Between	0.569	Likely Pathogenic	Likely Benign	3.10	Destabilizing	1.1	-1.08	Ambiguous	1.01	Ambiguous	0.52	Ambiguous	0.572	Likely Pathogenic	-1.05	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	1.32	Pathogenic	0.09	Tolerated			0.1938	0.1235		1	-1	-3.1	58.04
c.1127G>T	G376V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G376V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split assessment: benign predictions come from premPS, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized, while pathogenic predictions arise from REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The consensus score from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, matching the majority of individual benign calls. High‑accuracy methods give mixed results: AlphaMissense‑Optimized predicts benign, SGM Consensus predicts benign, whereas Foldetta (integrating FoldX‑MD and Rosetta) predicts pathogenic. No prediction is missing or inconclusive. Overall, the balance of evidence leans toward a benign effect; this is consistent with the lack of ClinVar annotation and gnomAD presence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.680603	Disordered	0.428979	Uncertain	0.326	0.869	0.625											-6.242	Likely Benign	0.120	Likely Benign	Likely Benign	4.84	Destabilizing	0.8	-0.81	Ambiguous	2.02	Destabilizing	-0.18	Likely Benign	0.541	Likely Pathogenic	-0.66	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	1.32	Pathogenic	0.01	Affected			0.1594	0.3525		-1	-3	4.6	42.08
c.1214G>T	R405L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R405L missense change is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are Rosetta and FATHMM, while the majority of other in silico predictors (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) indicate a pathogenic or likely pathogenic impact. Uncertain results come from FoldX, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labeling it likely pathogenic, and Foldetta providing an inconclusive stability prediction. Overall, the preponderance of evidence points to a pathogenic effect for R405L, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.404888	Uncertain	0.949	0.315	0.000											-11.576	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	1.43	Ambiguous	0.7	0.40	Likely Benign	0.92	Ambiguous	0.72	Ambiguous	0.512	Likely Pathogenic	-6.35	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.64	Benign	0.01	Affected			0.2126	0.5555		-3	-2	8.3	-43.03
c.1235T>G	L412W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L412W is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy methods further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.122885	Structured	0.331108	Uncertain	0.937	0.196	0.000											-13.436	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	8.44	Destabilizing	0.4	9.91	Destabilizing	9.18	Destabilizing	1.65	Destabilizing	0.503	Likely Pathogenic	-5.53	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.19	Benign	0.00	Affected			0.0586	0.2664		-2	-2	-4.7	73.05
c.1237C>T	P413S 2D 3DClick to see structure in 3D Viewer AISynGAP1 P413S is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include only FATHMM. All other evaluated predictors—SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and Foldetta—indicate a pathogenic effect. High‑accuracy methods give a consistent pathogenic verdict: AlphaMissense‑Optimized predicts pathogenicity, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic, and Foldetta (which integrates FoldX‑MD and Rosetta outputs) predicts pathogenic; FoldX alone supports pathogenicity while Rosetta remains uncertain. Taken together, the overwhelming majority of predictions support a pathogenic classification, and this is not contradicted by the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.332472	Uncertain	0.927	0.201	0.000											-12.586	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.06	Destabilizing	0.1	1.72	Ambiguous	2.39	Destabilizing	0.93	Ambiguous	0.509	Likely Pathogenic	-7.37	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.19	Benign	0.04	Affected			0.3454	0.3819		1	-1	0.8	-10.04
c.1238C>A	P413H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P413H is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include only FATHMM, while the remaining tools—SGM‑Consensus, REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic or likely pathogenic impact; Rosetta is uncertain. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No predictions are missing or inconclusive. Based on the overwhelming agreement among pathogenic predictors and the high‑accuracy tools, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.332472	Uncertain	0.927	0.201	0.000											-13.376	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	4.89	Destabilizing	1.0	1.85	Ambiguous	3.37	Destabilizing	1.07	Destabilizing	0.546	Likely Pathogenic	-8.29	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.16	Benign	0.00	Affected			0.1745	0.3480		0	-2	-1.6	40.02
c.1238C>G	P413R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P413R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The remaining methods, Foldetta and Rosetta, yield uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.332472	Uncertain	0.927	0.201	0.000											-15.523	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.40	Destabilizing	0.2	1.34	Ambiguous	1.87	Ambiguous	1.07	Destabilizing	0.562	Likely Pathogenic	-8.29	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.32	Benign	0.01	Affected			0.1550	0.2199		0	-2	-2.9	59.07
c.1238C>T	P413L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P413L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM. Those that predict a pathogenic effect comprise SGM‑Consensus, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Rosetta and Foldetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.332472	Uncertain	0.927	0.201	0.000											-12.735	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.61	Destabilizing	0.4	1.34	Ambiguous	1.98	Ambiguous	0.30	Likely Benign	0.461	Likely Benign	-9.21	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.19	Benign	0.00	Affected			0.2056	0.5614		-3	-3	5.4	16.04
c.1254A>C	K418N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K418N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM. The majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Stability‑based methods (FoldX, Rosetta, premPS, Foldetta) are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence indicates that K418N is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.360134	Uncertain	0.948	0.263	0.000											-13.310	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.57	Ambiguous	0.0	0.77	Ambiguous	0.67	Ambiguous	0.56	Ambiguous	0.132	Likely Benign	-4.41	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.04	Affected			0.3483	0.0606		1	0	0.4	-14.07
c.1254A>T	K418N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K418N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two consensus groups: benign predictions are provided by REVEL and FATHMM, whereas pathogenic predictions are given by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus score (Likely Pathogenic). Stability‑based methods FoldX, Rosetta, Foldetta, and premPS returned uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, and Foldetta’s stability analysis is inconclusive. Overall, the majority of reliable predictors classify K418N as pathogenic, and this conclusion does not contradict the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.360134	Uncertain	0.948	0.263	0.000											-13.310	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.57	Ambiguous	0.0	0.77	Ambiguous	0.67	Ambiguous	0.56	Ambiguous	0.132	Likely Benign	-4.41	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.04	Affected			0.3483	0.0606		1	0	0.4	-14.07
c.1286G>T	R429L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R429L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. No contradictory evidence is present from ClinVar or gnomAD. **Based on the aggregate predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.074921	Structured	0.390504	Uncertain	0.959	0.290	0.000											-6.495	Likely Benign	0.408	Ambiguous	Likely Benign	-0.05	Likely Benign	0.1	0.06	Likely Benign	0.01	Likely Benign	-0.12	Likely Benign	0.241	Likely Benign	-1.20	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	3.59	Benign	0.37	Tolerated			0.1555	0.4025		-3	-2	8.3	-43.03
c.1292T>C	L431P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L431P (ClinVar ID 661045.0) is reported as Pathogenic and is not present in gnomAD. Prediction tools that classify the variant as benign include only FATHMM. All other evaluated tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict it to be pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Pathogenic. Based on the overwhelming consensus of pathogenic predictions and the ClinVar designation, the variant is most likely pathogenic, with no contradiction to its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.094817	Structured	0.374755	Uncertain	0.959	0.300	0.000					Likely Pathogenic		1				-14.222	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	6.78	Destabilizing	0.3	11.59	Destabilizing	9.19	Destabilizing	2.29	Destabilizing	0.659	Likely Pathogenic	-6.39	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.91	Benign	0.05	Affected	3.37	29	0.3484	0.2163		-3	-3	-5.4	-16.04	222.4	62.8	0.1	0.0	0.1	0.0	X							Potentially Pathogenic	The iso-butyl side chain of Leu431, located in an α helix (res. Met414-Glu436), packs against other hydrophobic residues in an interhelix space (e.g., Val434, Leu435, Leu696, Leu711) in the WT simulations. While the backbone amide group of Leu431 forms an H-bond with the carbonyl group of His427, the cyclic five-membered pyrrolidine ring of Pro431, lacking the necessary amide group, cannot do the same. Thus, although the cyclic five-membered pyrrolidine ring of Pro431 packs almost as favorably as the side chain of Leu431 in the hydrophobic niche, the residue swap causes the α helix to partially unfold in the variant simulations.
c.1294T>A	C432S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C432S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools (SGM Consensus, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show SGM Consensus as likely pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic classification for C432S, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.362533	Uncertain	0.960	0.285	0.000											-8.229	Likely Pathogenic	0.913	Likely Pathogenic	Ambiguous	0.61	Ambiguous	0.1	0.96	Ambiguous	0.79	Ambiguous	1.52	Destabilizing	0.496	Likely Benign	-9.55	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.53	Benign	0.12	Tolerated			0.4262	0.1415		0	-1	-3.3	-16.06
c.1295G>C	C432S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C432S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools (SGM Consensus, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show SGM Consensus as likely pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic classification for C432S, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.362533	Uncertain	0.960	0.285	0.000											-8.229	Likely Pathogenic	0.913	Likely Pathogenic	Ambiguous	0.61	Ambiguous	0.1	0.96	Ambiguous	0.79	Ambiguous	1.52	Destabilizing	0.417	Likely Benign	-9.55	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.53	Benign	0.12	Tolerated			0.4262	0.1415		0	-1	-3.3	-16.06
c.1304T>G	L435W 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L435W is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM. The majority of other in silico predictors (REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) classify the change as pathogenic, and the SGM‑Consensus score is “Likely Pathogenic.” High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, while Foldetta’s stability analysis is inconclusive. Overall, the computational evidence strongly favors a pathogenic effect, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.229226	Structured	0.333584	Uncertain	0.954	0.292	0.000					Uncertain		1				-14.889	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	2.11	Destabilizing	0.1	0.69	Ambiguous	1.40	Ambiguous	1.66	Destabilizing	0.572	Likely Pathogenic	-5.63	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.15	Benign	0.00	Affected	3.37	29	0.0536	0.2496		-2	-2	-4.7	73.05	242.2	-25.2	0.0	0.0	0.3	0.1							X	Potentially Pathogenic	The iso-butyl side chain of Leu435, located in an α helix (res. Met414-Glu436), packs against other hydrophobic residues in an interhelix space (e.g., Val699, Val447, Leu489, Leu439) in the WT simulations. In the variant simulations, the indole ring of Trp435 fits into the same niche despite its considerably bulkier size. Additionally, the side chain forms an H-bond with the backbone carbonyl of Leu696 in an α helix (res. Asp684-Gln702). Although no apparent negative changes are observed during the variant simulation, the size difference between the swapped residues could affect the protein folding process.
c.1309C>G	P437A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P437A missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include REVEL, Rosetta, FATHMM, AlphaMissense‑Optimized, and premPS. Those that predict pathogenicity are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Tools with uncertain or inconclusive results are AlphaMissense‑Default, FoldX, and Foldetta. High‑accuracy assessments give AlphaMissense‑Optimized a benign prediction. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default (uncertain), ESM1b (pathogenic), FATHMM (benign), and PROVEAN (pathogenic), yields a pathogenic consensus. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is uncertain. Overall, the balance of evidence leans toward a pathogenic effect for P437A, and this conclusion does not contradict the current ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.175930	Structured	0.306196	Uncertain	0.921	0.298	0.000											-12.059	Likely Pathogenic	0.392	Ambiguous	Likely Benign	1.23	Ambiguous	0.0	-3.14	Stabilizing	-0.96	Ambiguous	0.50	Likely Benign	0.266	Likely Benign	-6.53	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	3.51	Benign	0.03	Affected			0.3489	0.4775		1	-1	3.4	-26.04
c.1375G>A	G459S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G459S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign calls come from REVEL and FATHMM, while pathogenic predictions are made by FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). Uncertain results are reported by Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as inconclusive, SGM‑Consensus as Likely Pathogenic, and Foldetta as inconclusive. Overall, the majority of evidence points to a pathogenic impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.185198	Structured	0.289888	Uncertain	0.903	0.150	0.125											-10.979	Likely Pathogenic	0.873	Likely Pathogenic	Ambiguous	2.34	Destabilizing	0.1	0.77	Ambiguous	1.56	Ambiguous	0.60	Ambiguous	0.414	Likely Benign	-5.46	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.09	Benign	0.05	Affected			0.2340	0.5197		1	0	-0.4	30.03
c.1380G>C	K460N 2D AIThe SynGAP1 missense variant K460N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, SIFT, and FATHMM, whereas those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a pathogenic signal: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic; and the protein‑folding stability method Foldetta, which integrates FoldX‑MD and Rosetta outputs, indicates a benign effect. Overall, the balance of evidence—six pathogenic versus five benign predictions, a pathogenic SGM Consensus, and a pathogenic AlphaMissense‑Optimized—suggests that K460N is most likely pathogenic. This conclusion does not contradict ClinVar status, as the variant is not currently catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.289547	Uncertain	0.938	0.150	0.125											-11.988	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.25	Likely Benign	0.5	0.45	Likely Benign	0.35	Likely Benign	0.89	Ambiguous	0.202	Likely Benign	-4.13	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.29	Benign	0.06	Tolerated			0.3669	0.1599		1	0	0.4	-14.07
c.1380G>T	K460N 2D AIThe SynGAP1 K460N missense variant is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus methods further support a pathogenic interpretation: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also pathogenic; whereas Foldetta, which integrates FoldX‑MD and Rosetta outputs, indicates a benign effect. Overall, the majority of evidence—including the high‑accuracy tools—points to a pathogenic impact for K460N. This conclusion is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.289547	Uncertain	0.938	0.150	0.125											-11.988	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.25	Likely Benign	0.5	0.45	Likely Benign	0.35	Likely Benign	0.89	Ambiguous	0.202	Likely Benign	-4.13	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.29	Benign	0.06	Tolerated			0.3669	0.1599		1	0	0.4	-14.07
c.1386G>C	K462N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K462N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are returned by PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts Pathogenic, and the SGM Consensus also indicates Likely Pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result, providing no definitive evidence. Overall, the majority of high‑confidence predictors lean toward pathogenicity, contradicting the absence of a ClinVar classification. Thus, the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.297737	Uncertain	0.921	0.159	0.125											-12.823	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.69	Ambiguous	0.1	1.67	Ambiguous	1.18	Ambiguous	0.90	Ambiguous	0.304	Likely Benign	-4.83	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.07	Tolerated	3.37	34	0.3967	0.1242		0	1	0.4	-14.07
c.1386G>T	K462N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K462N is reported in gnomAD (ID 6‑33438291‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions from REVEL, SIFT, and FATHMM; pathogenic predictions from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Stability‑based methods (FoldX, Rosetta, premPS) and Foldetta are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM Consensus as likely pathogenic, while Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for K462N. This conclusion is not contradicted by ClinVar, which contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.297737	Uncertain	0.921	0.159	0.125								6-33438291-G-T	1	6.20e-7	-12.823	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.69	Ambiguous	0.1	1.67	Ambiguous	1.18	Ambiguous	0.90	Ambiguous	0.303	Likely Benign	-4.83	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.07	Tolerated	3.37	34	0.3967	0.1242		0	1	0.4	-14.07
c.1394T>G	L465R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L465R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect. Benign predictions: none. Pathogenic predictions: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenic. No inconclusive or missing results are present. Based on the consensus of all available predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.346032	Structured	0.319240	Uncertain	0.956	0.202	0.000											-17.976	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	4.52	Destabilizing	0.7	4.44	Destabilizing	4.48	Destabilizing	2.41	Destabilizing	0.761	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.29	Pathogenic	0.00	Affected			0.1597	0.0963		-3	-2	-8.3	43.03
c.1399G>C	D467H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D467H is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include only premPS, whereas the remaining evaluated algorithms uniformly predict a pathogenic impact: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta yield uncertain results and are treated as unavailable. High‑accuracy assessments reinforce the pathogenic prediction: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also pathogenic; Foldetta remains uncertain. Overall, the variant is most likely pathogenic based on the consensus of the available predictions, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.329932	Uncertain	0.940	0.246	0.000											-13.348	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	1.05	Ambiguous	0.1	0.59	Ambiguous	0.82	Ambiguous	0.32	Likely Benign	0.851	Likely Pathogenic	-6.71	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.31	Pathogenic	0.02	Affected			0.1074	0.5564		1	-1	0.3	22.05
c.1400A>C	D467A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D467A missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include premPS and SIFT, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools with uncertain or inconclusive results—FoldX, Rosetta, and Foldetta—do not provide decisive evidence. High‑accuracy assessments reinforce the pathogenic prediction: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the current ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.329932	Uncertain	0.940	0.246	0.000											-12.499	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	0.83	Ambiguous	0.1	0.79	Ambiguous	0.81	Ambiguous	0.23	Likely Benign	0.790	Likely Pathogenic	-7.71	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.19	Pathogenic	0.07	Tolerated			0.3134	0.5117		0	-2	5.3	-44.01
c.1415A>C	E472A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E472A is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a pathogenic effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; all these methods uniformly classify the change as deleterious. Tools that are inconclusive or uncertain for this variant are FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts a pathogenic outcome, the SGM Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates pathogenicity, while Foldetta’s stability analysis remains uncertain. Taken together, the overwhelming majority of evidence points to a pathogenic effect for E472A, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.359300	Uncertain	0.878	0.231	0.000											-15.356	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	1.81	Ambiguous	0.3	0.67	Ambiguous	1.24	Ambiguous	0.69	Ambiguous	0.732	Likely Pathogenic	-5.90	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.32	Pathogenic	0.01	Affected			0.4639	0.6315		0	-1	5.3	-58.04
c.1415A>G	E472G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E472G is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that assess the variant’s effect largely agree on a deleterious outcome: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic or likely pathogenic. Only premPS predicts a benign effect. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized reports pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. No predictions are missing or inconclusive. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.359300	Uncertain	0.878	0.231	0.000											-15.239	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	3.06	Destabilizing	0.2	2.86	Destabilizing	2.96	Destabilizing	0.24	Likely Benign	0.744	Likely Pathogenic	-6.83	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.30	Pathogenic	0.00	Affected			0.3343	0.4950		0	-2	3.1	-72.06
c.1420G>C	D474H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D474H is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include Rosetta, Foldetta, and premPS, whereas the majority of tools predict it to be pathogenic: REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score of Likely Pathogenic. High‑accuracy methods give mixed results: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, reports a benign effect. Overall, the preponderance of evidence points to a pathogenic effect for D474H, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.373433	Uncertain	0.864	0.255	0.000											-13.610	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.66	Ambiguous	0.0	0.00	Likely Benign	0.33	Likely Benign	0.27	Likely Benign	0.739	Likely Pathogenic	-5.93	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.32	Pathogenic	0.02	Affected			0.1398	0.4619		1	-1	0.3	22.05
c.1421A>C	D474A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D474A missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from FoldX, Rosetta, Foldetta, premPS, and SIFT, while pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as Pathogenic, SGM Consensus as Likely Pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.373433	Uncertain	0.864	0.255	0.000											-11.082	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	0.08	Likely Benign	0.0	0.15	Likely Benign	0.12	Likely Benign	0.17	Likely Benign	0.757	Likely Pathogenic	-6.73	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.22	Pathogenic	0.22	Tolerated			0.3265	0.4354		0	-2	5.3	-44.01
c.1439A>C	E480A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E480A is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only SIFT, whereas a majority of tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from the four pathogenic‑predicted tools above) as likely pathogenic, and Foldetta as uncertain. Because most evidence points to a deleterious effect, the variant is most likely pathogenic, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.216401	Structured	0.426867	Uncertain	0.798	0.250	0.000											-13.192	Likely Pathogenic	0.931	Likely Pathogenic	Ambiguous	0.91	Ambiguous	0.1	1.15	Ambiguous	1.03	Ambiguous	0.55	Ambiguous	0.694	Likely Pathogenic	-5.04	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.25	Pathogenic	0.09	Tolerated			0.3468	0.6635		0	-1	5.3	-58.04
c.1439A>G	E480G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E480G missense variant is not reported in ClinVar and has no gnomAD entry. Consensus from multiple in‑silico predictors indicates a pathogenic effect: SGM‑Consensus, REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify it as pathogenic. Predictions that are uncertain—FoldX, premPS, and AlphaMissense‑Optimized—do not provide evidence for benignity. High‑accuracy assessments further support pathogenicity: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic, and AlphaMissense‑Optimized remains uncertain. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because no ClinVar record exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.216401	Structured	0.426867	Uncertain	0.798	0.250	0.000											-11.651	Likely Pathogenic	0.839	Likely Pathogenic	Ambiguous	1.83	Ambiguous	0.1	2.34	Destabilizing	2.09	Destabilizing	0.65	Ambiguous	0.778	Likely Pathogenic	-5.44	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.32	Pathogenic	0.03	Affected			0.2806	0.6172		0	-2	3.1	-72.06
c.1454G>A	R485H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R485H missense variant is listed in ClinVar as Benign (ClinVar ID 3707943.0) and is present in the gnomAD database (gnomAD ID 6‑33438486‑G‑A). Functional prediction tools that agree on a benign effect are Rosetta and Foldetta, while the majority of tools (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the preponderance of evidence points to a pathogenic effect, which contradicts the ClinVar benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.188120	Structured	0.377409	Uncertain	0.805	0.246	0.125					Likely Benign		1	6-33438486-G-A	13	8.05e-6	-13.628	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous	0.77	Ambiguous	0.1	0.12	Likely Benign	0.45	Likely Benign	1.13	Destabilizing	0.618	Likely Pathogenic	-4.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.93	Pathogenic	0.00	Affected	3.37	35	0.2990	0.1602		0	2	1.3	-19.05
c.1457A>C	E486A 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E486A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, Rosetta, premPS, SIFT, and FATHMM, whereas pathogenic predictions are made by SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive and therefore unavailable. Overall, the majority of evidence supports a pathogenic effect. The prediction aligns with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.196879	Structured	0.358545	Uncertain	0.833	0.245	0.125											-11.902	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	0.63	Ambiguous	0.0	0.32	Likely Benign	0.48	Likely Benign	-0.03	Likely Benign	0.398	Likely Benign	-5.17	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	3.44	Benign	0.39	Tolerated			0.3561	0.5859		0	-1	5.3	-58.04
c.1457A>G	E486G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E486G missense change is not listed in ClinVar and has no gnomAD entry. Functional prediction tools that agree on a benign effect include REVEL, premPS, SIFT, and FATHMM. Those that predict a damaging outcome are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. Predictions from FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of evidence points toward a pathogenic effect. This conclusion is consistent with the absence of a ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.196879	Structured	0.358545	Uncertain	0.833	0.245	0.125											-12.488	Likely Pathogenic	0.924	Likely Pathogenic	Ambiguous	1.09	Ambiguous	0.1	1.59	Ambiguous	1.34	Ambiguous	-0.14	Likely Benign	0.328	Likely Benign	-5.46	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.80	Benign	0.40	Tolerated			0.2918	0.5385		0	-2	3.1	-72.06
c.1459A>T	N487Y 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N487Y has no ClinVar entry and is absent from gnomAD. Prediction tools that classify it as benign include Rosetta, premPS, and FATHMM, whereas the majority of algorithms—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—label it pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports it as likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. Overall, the preponderance of evidence points to a pathogenic impact for N487Y, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.209395	Structured	0.338511	Uncertain	0.890	0.243	0.125											-14.921	Likely Pathogenic	0.967	Likely Pathogenic	Likely Pathogenic	1.15	Ambiguous	0.0	-0.05	Likely Benign	0.55	Ambiguous	0.33	Likely Benign	0.652	Likely Pathogenic	-7.96	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.69	Benign	0.00	Affected			0.0587	0.2946		-2	-2	2.2	49.07
c.1460A>T	N487I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N487I has no ClinVar entry and is not reported in gnomAD. Functional prediction tools largely disagree, but the majority indicate a deleterious effect. Benign predictions come from Rosetta, premPS, and FATHMM, whereas pathogenic predictions are reported by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results are provided by FoldX and Foldetta. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also predicts pathogenic; Foldetta remains inconclusive. Overall, the preponderance of evidence supports a pathogenic classification for N487I, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.209395	Structured	0.338511	Uncertain	0.890	0.243	0.125											-16.592	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	1.71	Ambiguous	0.1	0.13	Likely Benign	0.92	Ambiguous	0.33	Likely Benign	0.591	Likely Pathogenic	-8.95	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.67	Benign	0.00	Affected			0.0633	0.3531		-2	-3	8.0	-0.94
c.1462A>T	T488S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T488S missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Four tools (Foldetta, premPS, ESM1b, and Rosetta) return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of standard tools lean toward a benign interpretation, but the high‑accuracy consensus is split, leaving the variant’s impact ambiguous. No ClinVar annotation contradicts these predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.206376	Structured	0.332663	Uncertain	0.928	0.233	0.125											-7.662	In-Between	0.745	Likely Pathogenic	Likely Benign	0.35	Likely Benign	0.1	0.90	Ambiguous	0.63	Ambiguous	0.77	Ambiguous	0.257	Likely Benign	-3.51	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	3.73	Benign	0.31	Tolerated			0.2256	0.2813		1	1	-0.1	-14.03
c.1466T>G	L489R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L489R is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity are unanimous: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool in the dataset predicts a benign effect. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized indicates pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a destabilizing, pathogenic effect. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which simply lacks an entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.191378	Structured	0.326126	Uncertain	0.949	0.234	0.125											-15.365	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	4.32	Destabilizing	0.3	4.90	Destabilizing	4.61	Destabilizing	1.74	Destabilizing	0.949	Likely Pathogenic	-5.86	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.61	Pathogenic	0.00	Affected			0.1306	0.1145		-3	-2	-8.3	43.03
c.1468G>C	A490P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A490P is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Among the available in‑silico predictors, 10 tools (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) uniformly predict a pathogenic effect, whereas only Foldetta predicts a benign outcome; FoldX, Rosetta, and AlphaMissense‑Optimized are inconclusive. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta stability outputs) is benign. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.120615	Structured	0.322979	Uncertain	0.938	0.210	0.125					Uncertain		1				-12.905	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	-1.27	Ambiguous	0.1	1.31	Ambiguous	0.02	Likely Benign	1.07	Destabilizing	0.878	Likely Pathogenic	-4.81	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.42	Pathogenic	0.01	Affected	3.37	35	0.1755	0.3071		-1	1	-3.4	26.04
c.1469C>A	A490D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A490D is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that assess pathogenicity are unanimous: AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, FATHMM, PROVEAN, SIFT, polyPhen‑2 (HumDiv and HumVar), REVEL, premPS, FoldX, Rosetta, and Foldetta all classify the variant as pathogenic. No tool predicts a benign effect, so the benign group is empty. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports pathogenic. Based on the collective predictions, the variant is most likely pathogenic, and this assessment is consistent with the absence of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.120615	Structured	0.322979	Uncertain	0.938	0.210	0.125											-16.643	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	3.33	Destabilizing	0.1	4.23	Destabilizing	3.78	Destabilizing	1.33	Destabilizing	0.946	Likely Pathogenic	-5.70	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.48	Pathogenic	0.00	Affected			0.1532	0.1741		0	-2	-5.3	44.01
c.1471A>T	T491S 2D AIThe SynGAP1 missense variant T491S is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include only SIFT, whereas the majority of tools predict a pathogenic impact: REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. No evidence from FoldX or Rosetta is available to support a stability change. Overall, the preponderance of evidence points to a pathogenic effect for T491S, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.064632	Structured	0.325158	Uncertain	0.929	0.188	0.125											-7.273	In-Between	0.924	Likely Pathogenic	Ambiguous	0.93	Ambiguous	0.7	1.27	Ambiguous	1.10	Ambiguous	1.00	Destabilizing	0.704	Likely Pathogenic	-3.90	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.25	Pathogenic	0.19	Tolerated			0.3119	0.2815		1	1	-0.1	-14.03
c.1472C>G	T491S 2D AIThe SynGAP1 missense variant T491S is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include only SIFT, whereas the majority of tools predict a pathogenic impact: REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. No evidence from FoldX or Rosetta is available to support a stability change. Overall, the preponderance of evidence points to a pathogenic effect for T491S, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.064632	Structured	0.325158	Uncertain	0.929	0.188	0.125											-7.273	In-Between	0.924	Likely Pathogenic	Ambiguous	0.93	Ambiguous	0.7	1.27	Ambiguous	1.10	Ambiguous	1.00	Destabilizing	0.666	Likely Pathogenic	-3.90	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.25	Pathogenic	0.19	Tolerated			0.3119	0.2815		1	1	-0.1	-14.03
c.1474A>G	K492E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K492E is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that classify the variant as benign include only FATHMM. The remaining tools—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict it to be pathogenic or likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores it as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, which contradicts its current ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.327121	Uncertain	0.947	0.192	0.000					Conflicting		2				-16.175	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.53	Ambiguous	0.1	1.90	Ambiguous	1.72	Ambiguous	1.42	Destabilizing	0.510	Likely Pathogenic	-3.98	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.99	Benign	0.01	Affected	3.37	35	0.2968	0.0650		1	0	0.4	0.94
c.1477G>C	A493P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A493P is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess functional impact all converge on a pathogenic interpretation: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict deleterious effects. No tool in the dataset indicates a benign outcome. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. With all available evidence pointing to a damaging effect and no ClinVar entry to contradict, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.340081	Uncertain	0.966	0.182	0.000											-15.797	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	4.96	Destabilizing	0.1	10.79	Destabilizing	7.88	Destabilizing	1.32	Destabilizing	0.883	Likely Pathogenic	-4.54	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.41	Pathogenic	0.02	Affected			0.1490	0.2907		1	-1	-3.4	26.04
c.1478C>A	A493D 2D AISynGAP1 missense variant A493D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as pathogenic. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. Consequently, the variant is most likely pathogenic, and this assessment is consistent with the absence of a ClinVar entry (no contradiction). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.340081	Uncertain	0.966	0.182	0.000											-16.834	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	4.45	Destabilizing	1.5	3.59	Destabilizing	4.02	Destabilizing	1.60	Destabilizing	0.925	Likely Pathogenic	-5.25	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.41	Pathogenic	0.01	Affected			0.1437	0.1541		0	-2	-5.3	44.01
c.1499T>G	L500R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L500R is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as pathogenic include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool predicts a benign effect; the benign group is empty. Predictions that are uncertain or inconclusive are Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Based on the overwhelming agreement among pathogenic predictors and the lack of any benign calls, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status (which has no entry). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.066181	Structured	0.382942	Uncertain	0.893	0.150	0.000											-15.576	Likely Pathogenic	0.789	Likely Pathogenic	Ambiguous	2.23	Destabilizing	0.1	1.04	Ambiguous	1.64	Ambiguous	1.11	Destabilizing	0.794	Likely Pathogenic	-5.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.02	Pathogenic	0.03	Affected			0.1204	0.0488		-3	-2	-8.3	43.03
c.1517T>G	L506R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L506R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Pathogenic. Thus, all available evidence indicates that the variant is most likely pathogenic, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.034884	Structured	0.279180	Uncertain	0.924	0.196	0.000											-14.119	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	4.92	Destabilizing	0.6	5.85	Destabilizing	5.39	Destabilizing	1.77	Destabilizing	0.738	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.54	Pathogenic	0.00	Affected			0.1207	0.0488		-3	-2	-8.3	43.03
c.1532G>C	G511A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G511A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, Rosetta, and FATHMM, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Uncertain results are reported by FoldX, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is inconclusive, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta remains uncertain. Overall, the balance of evidence (seven pathogenic versus three benign predictions) indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.244404	Uncertain	0.924	0.287	0.000											-9.621	Likely Pathogenic	0.844	Likely Pathogenic	Ambiguous	0.80	Ambiguous	0.2	0.25	Likely Benign	0.53	Ambiguous	0.55	Ambiguous	0.275	Likely Benign	-5.73	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	3.23	Benign	0.02	Affected			0.3793	0.2778		1	0	2.2	14.03
c.1537T>G	F513V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F513V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only SIFT, whereas the remaining tools—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the overwhelming agreement among these predictions, the variant is most likely pathogenic, and this conclusion does not contradict the current ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.250651	Uncertain	0.949	0.269	0.000											-10.675	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	3.54	Destabilizing	0.4	2.68	Destabilizing	3.11	Destabilizing	1.13	Destabilizing	0.799	Likely Pathogenic	-6.70	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.21	Pathogenic	0.44	Tolerated			0.1656	0.1583		-1	-1	1.4	-48.04
c.1544G>A	R515H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R515H is listed in ClinVar with an uncertain significance (ClinVar ID 638438.0) and is present in gnomAD (variant ID 6‑33438787‑G‑A). Prediction tools that agree on a benign effect include AlphaMissense‑Default and AlphaMissense‑Optimized. Those that predict a pathogenic impact comprise REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus remains pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive. Overall, the balance of evidence favors a pathogenic effect, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.055536	Structured	0.191256	Uncertain	0.924	0.275	0.000					Uncertain		1	6-33438787-G-A	3	1.86e-6	-10.774	Likely Pathogenic	0.337	Likely Benign	Likely Benign	1.07	Ambiguous	0.2	0.74	Ambiguous	0.91	Ambiguous	1.09	Destabilizing	0.730	Likely Pathogenic	-3.44	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.32	Pathogenic	0.01	Affected	3.37	35	0.2343	0.0746		2	0	1.3	-19.05	239.2	77.8	0.0	0.0	0.4	0.2		X						Potentially Benign	The guanidinium group of Arg515, located in the middle of an α-helix at the GAP domain (res. Gly502-Tyr518), forms salt bridges with the carboxylate groups of Glu512 on the same helix and Glu217 on a loop in the PH domain. Additionally, the positively charged Arg515 side chain forms hydrogen bonds with Leu610 and Gln612 in an opposing loop (res. Gly609-Asp616). In contrast, in the variant simulations, the imidazole ring of His515 cannot form salt bridges with either of the acidic residues, and its side chain is too short to form hydrogen bonds with the loop residues. Accordingly, the residue swap could weaken the tertiary structure assembly of the protein. Due to the missing N-terminal part of the SynGAP model, the effect could be largely underestimated or missing. Notably, the doubly protonated and positively charged form of histidine was not simulated here.
c.1546G>C	A516P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A516P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only SIFT, whereas the remaining tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact; premPS is inconclusive. High‑accuracy methods further support pathogenicity: AlphaMissense‑Optimized scores it as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) classifies it as pathogenic. Based on the consensus of these predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.167423	Uncertain	0.938	0.284	0.000											-15.348	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.67	Destabilizing	0.3	10.96	Destabilizing	6.82	Destabilizing	0.83	Ambiguous	0.750	Likely Pathogenic	-4.41	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.29	Pathogenic	0.06	Tolerated			0.2214	0.4328		1	-1	-3.4	26.04
c.1547C>A	A516D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A516D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only SIFT, which scores the substitution as tolerated. In contrast, the majority of algorithms predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Uncertain or inconclusive results come from FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is likely pathogenic, while Foldetta remains uncertain. Overall, the preponderance of evidence indicates that A516D is most likely pathogenic, and this conclusion does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.167423	Uncertain	0.938	0.284	0.000											-14.621	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.65	Ambiguous	0.2	1.04	Ambiguous	0.85	Ambiguous	0.62	Ambiguous	0.725	Likely Pathogenic	-5.17	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.23	Pathogenic	0.15	Tolerated			0.1890	0.1679		0	-2	-5.3	44.01
c.1550T>G	L517R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L517R is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; the only tool with an uncertain outcome is FoldX. High‑accuracy methods give consistent results: AlphaMissense‑Optimized predicts Pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts Likely Pathogenic, and Foldetta predicts Pathogenic. Based on the overwhelming agreement among these predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.118441	Structured	0.147645	Uncertain	0.938	0.296	0.000											-14.761	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	1.75	Ambiguous	0.2	4.33	Destabilizing	3.04	Destabilizing	1.83	Destabilizing	0.936	Likely Pathogenic	-5.79	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.50	Pathogenic	0.00	Affected			0.1202	0.0688		-3	-2	-8.3	43.03
c.1556A>C	E519A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E519A missense variant is listed in ClinVar as Pathogenic (ClinVar ID 1029087.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, premPS, SIFT, and FATHMM. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, ESM1b, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Uncertain predictions from Rosetta and AlphaMissense‑Optimized are treated as unavailable. High‑accuracy results are: AlphaMissense‑Optimized – unavailable; SGM‑Consensus – Pathogenic; Foldetta – Benign. Overall, the predictions are balanced, but the high‑accuracy Foldetta result leans toward benign while the consensus leans toward pathogenic, leaving the assessment inconclusive. Based on the available predictions, the variant is most likely benign, contradicting the ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.078022	Structured	0.104514	Uncertain	0.899	0.328	0.000					Likely Pathogenic		1				-8.557	Likely Pathogenic	0.904	Likely Pathogenic	Ambiguous	-0.05	Likely Benign	0.0	0.55	Ambiguous	0.25	Likely Benign	0.00	Likely Benign	0.384	Likely Benign	-5.23	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	3.33	Benign	0.10	Tolerated	3.37	35	0.3544	0.3545		0	-1	5.3	-58.04	162.4	83.5	-0.1	0.1	-0.2	0.0						X		Potentially Benign	Glu519 is located at the beginning of an α-α loop between the two α-helices (res. Gly502-Tyr518 and Ala533-Val560). In the WT simulations, the carboxylate side chain of Glu519 does not make any specific interactions. Accordingly, the Ala residue swap does not show any negative structural effects in the variant simulations. However, it should be noted that Glu519 faces the missing part of the N-terminal in the model, and thus its potential role in maintaining the tertiary structure might be de-emphasized in the current model.
c.1556A>G	E519G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E519G missense variant is not reported in ClinVar (ClinVar status: None) and has no entry in gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, and premPS. Tools that predict a pathogenic effect comprise SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. Uncertain predictions come from Foldetta, AlphaMissense‑Optimized, and Rosetta. High‑accuracy assessments: AlphaMissense‑Optimized is uncertain; SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic; Foldetta is uncertain. Overall, the majority of available predictions (7 pathogenic vs. 4 benign) lean toward a pathogenic impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.078022	Structured	0.104514	Uncertain	0.899	0.328	0.000											-10.835	Likely Pathogenic	0.884	Likely Pathogenic	Ambiguous	0.22	Likely Benign	0.1	0.92	Ambiguous	0.57	Ambiguous	0.22	Likely Benign	0.458	Likely Benign	-6.12	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.21	Benign	0.01	Affected			0.2729	0.3471		0	-2	3.1	-72.06
c.1570T>C	C524R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C524R is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Across the evaluated in‑silico tools, all pathogenic‑predicating algorithms—REVEL, SGM‑Consensus, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—return a pathogenic or likely pathogenic verdict. The only tool with an inconclusive result is FoldX, which is treated as unavailable. High‑accuracy predictors reinforce this assessment: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, also predicts pathogenic. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.024729	Uncertain	0.916	0.385	0.125											-14.337	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	-0.53	Ambiguous	0.5	9.04	Destabilizing	4.26	Destabilizing	1.62	Destabilizing	0.917	Likely Pathogenic	-11.93	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.40	Pathogenic	0.00	Affected			0.2031	0.1463		-4	-3	-7.0	53.05
c.1571G>A	C524Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C524Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess the variant’s effect largely agree on a deleterious outcome: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic, while premPS is the sole tool predicting a benign effect. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. With the overwhelming majority of evidence pointing to a damaging effect and no ClinVar annotation to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.024729	Uncertain	0.916	0.385	0.125											-11.032	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.20	Destabilizing	1.4	6.24	Destabilizing	4.72	Destabilizing	0.18	Likely Benign	0.863	Likely Pathogenic	-10.94	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.36	Pathogenic	0.00	Affected			0.1496	0.3911		0	-2	-3.8	60.04
c.1571G>T	C524F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C524F is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that assess the variant’s effect largely agree on a deleterious outcome: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic, while only premPS predicts a benign effect. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized reports pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. No prediction or stability result is missing or inconclusive. Based on the overwhelming majority of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.024729	Uncertain	0.916	0.385	0.125											-12.145	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	2.18	Destabilizing	1.4	5.20	Destabilizing	3.69	Destabilizing	-0.04	Likely Benign	0.831	Likely Pathogenic	-10.94	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.22	Pathogenic	0.05	Affected			0.1678	0.4259		-4	-2	0.3	44.04
c.1574A>C	E525A 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E525A is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include Foldetta, premPS, and FATHMM, whereas the majority of other in silico predictors (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic effect. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled Likely Pathogenic, whereas Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a benign impact. Overall, the preponderance of evidence from both general and high‑accuracy tools points to a pathogenic classification for E525A, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.023618	Uncertain	0.937	0.382	0.125											-12.627	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	1.23	Ambiguous	0.6	-0.62	Ambiguous	0.31	Likely Benign	0.09	Likely Benign	0.680	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.68	Benign	0.00	Affected			0.3554	0.3960		0	-1	5.3	-58.04
c.1574A>G	E525G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E525G is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include only FATHMM. All other evaluated algorithms—REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—predict it to be pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized returns a pathogenic score, the SGM‑Consensus also indicates pathogenicity, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, yields an uncertain result. Taken together, the overwhelming majority of evidence points to a pathogenic impact for E525G. This conclusion is consistent with the absence of ClinVar annotation and gnomAD data, and there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.023618	Uncertain	0.937	0.382	0.125											-13.181	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.71	Ambiguous	0.6	0.90	Ambiguous	1.31	Ambiguous	0.78	Ambiguous	0.691	Likely Pathogenic	-6.96	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.68	Benign	0.00	Affected			0.2947	0.3886		0	-2	3.1	-72.06
c.1579G>C	D527H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D527H is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include FoldX and premPS, whereas the majority of tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict it to be pathogenic. Uncertain results come from Rosetta and Foldetta. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM Consensus as pathogenic, and Foldetta as inconclusive. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.021908	Uncertain	0.913	0.408	0.000											-13.334	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	0.40	Likely Benign	1.2	1.26	Ambiguous	0.83	Ambiguous	0.49	Likely Benign	0.901	Likely Pathogenic	-6.80	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-2.39	Pathogenic	0.00	Affected			0.1092	0.4346		1	-1	0.3	22.05
c.1580A>C	D527A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D527A missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only premPS, while the remaining evaluated methods (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict pathogenicity. FoldX, Rosetta, and Foldetta are inconclusive and are treated as unavailable. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta remains uncertain. Overall, the variant is most likely pathogenic based on the consensus of predictive tools, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.021908	Uncertain	0.913	0.408	0.000											-15.473	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	0.81	Ambiguous	0.9	1.75	Ambiguous	1.28	Ambiguous	-0.24	Likely Benign	0.929	Likely Pathogenic	-7.79	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-2.39	Pathogenic	0.00	Affected			0.2850	0.3799		0	-2	5.3	-44.01
c.1601C>A	S534Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S534Y has no ClinVar entry and is not reported in gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, FATHMM, premPS, AlphaMissense‑Optimized, and Foldetta, while those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen2_HumDiv, polyPhen2_HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta as benign. Overall, the majority of tools (seven versus six) lean toward a pathogenic effect, and the high‑accuracy consensus is split, leaving the variant’s impact uncertain. Based on the aggregate predictions, the variant is most likely pathogenic, which does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.167087	Structured	0.032173	Uncertain	0.860	0.362	0.000											-11.540	Likely Pathogenic	0.575	Likely Pathogenic	Likely Benign	-0.01	Likely Benign	0.1	0.66	Ambiguous	0.33	Likely Benign	0.46	Likely Benign	0.314	Likely Benign	-5.02	Deleterious	0.998	Probably Damaging	0.998	Probably Damaging	3.27	Benign	0.00	Affected			0.0629	0.5073		-3	-2	-0.5	76.10
c.1601C>T	S534F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S534F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include REVEL, FoldX, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. Tools with uncertain results are AlphaMissense‑Default and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic. Overall, the majority of predictions lean toward a benign effect, and this is consistent with the lack of ClinVar evidence; thus the variant is most likely benign and does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.167087	Structured	0.032173	Uncertain	0.860	0.362	0.000											-10.948	Likely Pathogenic	0.492	Ambiguous	Likely Benign	-0.03	Likely Benign	0.1	0.88	Ambiguous	0.43	Likely Benign	0.43	Likely Benign	0.313	Likely Benign	-5.09	Deleterious	0.998	Probably Damaging	0.998	Probably Damaging	3.26	Benign	0.00	Affected			0.0621	0.5379		-3	-2	3.6	60.10
c.1617C>A	H539Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H539Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include SIFT, FoldX, and Foldetta. Those that predict a pathogenic effect comprise SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain predictions come from AlphaMissense‑Optimized, Rosetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of tools (nine pathogenic vs. three benign) indicate a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.031398	Uncertain	0.948	0.360	0.000											-9.133	Likely Pathogenic	0.942	Likely Pathogenic	Ambiguous	-0.42	Likely Benign	0.0	0.92	Ambiguous	0.25	Likely Benign	0.89	Ambiguous	0.597	Likely Pathogenic	-7.05	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.21	Pathogenic	0.07	Tolerated			0.1052	0.2008		3	0	-0.3	-9.01
c.1617C>G	H539Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H539Q missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include SIFT, FoldX, and Foldetta. Those that predict a pathogenic effect comprise SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain predictions come from AlphaMissense‑Optimized, Rosetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of tools (nine pathogenic vs. three benign) and the SGM‑Consensus result support a pathogenic classification, while Foldetta suggests benign. No ClinVar entry exists to contradict these predictions, so the variant is most likely pathogenic based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.031398	Uncertain	0.948	0.360	0.000											-9.133	Likely Pathogenic	0.942	Likely Pathogenic	Ambiguous	-0.42	Likely Benign	0.0	0.92	Ambiguous	0.25	Likely Benign	0.89	Ambiguous	0.597	Likely Pathogenic	-7.05	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.21	Pathogenic	0.07	Tolerated			0.1052	0.2008		3	0	-0.3	-9.01
c.1621G>C	A541P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A541P is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that classify the variant as benign include only SIFT, whereas the remaining tools—REVEL, FoldX, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict it to be pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM Consensus is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenicity. No predictions are inconclusive or missing. Overall, the collective evidence points to a pathogenic effect for A541P, which is in contrast to the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.050641	Structured	0.029947	Uncertain	0.955	0.365	0.000					Uncertain		1				-14.733	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	2.47	Destabilizing	0.3	7.26	Destabilizing	4.87	Destabilizing	0.86	Ambiguous	0.594	Likely Pathogenic	-3.16	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.34	Pathogenic	0.07	Tolerated	3.37	35	0.1706	0.2707		1	-1	-3.4	26.04	170.4	-11.2	0.1	0.0	0.1	0.0	X							Potentially Pathogenic	Ala541 is located on the outer surface of an α-helix (res. Ala533-Val560). The methyl group of Ala541 is on the surface and does not form any interactions. Proline lacks a free backbone amide group, and thus, Pro541 is unable to form a hydrogen bond with the carbonyl group of Ala537 in the variant simulations. Consequently, Pro541 disrupts the continuity of the secondary structure element, causing the α-helix to bend slightly in the variant simulations.
c.1622C>A	A541D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A541D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SIFT and FoldX, whereas a larger group—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of evidence points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.050641	Structured	0.029947	Uncertain	0.955	0.365	0.000											-11.510	Likely Pathogenic	0.864	Likely Pathogenic	Ambiguous	0.36	Likely Benign	0.0	0.65	Ambiguous	0.51	Ambiguous	0.65	Ambiguous	0.571	Likely Pathogenic	-3.18	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.15	Pathogenic	0.14	Tolerated			0.1581	0.1902		0	-2	-5.3	44.01
c.1624A>C	N542H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N542H is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include FoldX, Rosetta, Foldetta, and premPS, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus—predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta as benign. Overall, the majority of evidence supports a pathogenic effect. Thus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.053060	Structured	0.026143	Uncertain	0.953	0.331	0.000											-10.983	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	0.06	Likely Benign	0.1	-0.12	Likely Benign	-0.03	Likely Benign	0.46	Likely Benign	0.791	Likely Pathogenic	-3.91	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.44	Pathogenic	0.05	Affected			0.1137	0.5368		2	1	0.3	23.04
c.1628T>G	L543R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L543R is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that assess pathogenicity all agree that the variant is deleterious: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic. No tool predicts a benign effect. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, indicates a pathogenic impact. All available predictions are concordant and supportive. Based on these computational assessments, the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.020918	Uncertain	0.963	0.314	0.000											-18.563	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.47	Destabilizing	1.2	8.02	Destabilizing	5.75	Destabilizing	1.64	Destabilizing	0.739	Likely Pathogenic	-5.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.89	Pathogenic	0.00	Affected			0.1229	0.0488		-3	-2	-8.3	43.03
c.1636T>C	C546R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C546R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include only SIFT, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX and Foldetta return uncertain results and are therefore not considered evidence for either side. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta as Uncertain. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.027463	Structured	0.009041	Uncertain	0.960	0.288	0.000											-15.237	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	-0.70	Ambiguous	0.3	2.04	Destabilizing	0.67	Ambiguous	1.70	Destabilizing	0.894	Likely Pathogenic	-9.73	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.26	Pathogenic	0.06	Tolerated			0.1808	0.1685		-4	-3	-7.0	53.05
c.1637G>A	C546Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C546Y is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that classify the variant as benign include FoldX, premPS, and SIFT, whereas the remaining tools—SGM‑Consensus, REVEL, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict it to be pathogenic. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized reports a pathogenic effect; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a destabilizing, pathogenic impact. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.027463	Structured	0.009041	Uncertain	0.960	0.288	0.000											-10.771	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	-0.08	Likely Benign	1.8	4.75	Destabilizing	2.34	Destabilizing	0.09	Likely Benign	0.794	Likely Pathogenic	-8.74	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.07	Pathogenic	0.29	Tolerated			0.1433	0.3015		0	-2	-3.8	60.04
c.1637G>T	C546F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant C546F is not reported in ClinVar and is absent from gnomAD. In silico predictors that classify the variant as benign include premPS and SIFT, whereas the majority of tools predict pathogenicity: REVEL, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus score (Likely Pathogenic). High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, SGM Consensus also indicates Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for C546F, and this assessment does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.027463	Structured	0.009041	Uncertain	0.960	0.288	0.000											-13.479	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	-1.21	Ambiguous	0.9	3.98	Destabilizing	1.39	Ambiguous	0.34	Likely Benign	0.800	Likely Pathogenic	-8.99	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.20	Pathogenic	0.12	Tolerated			0.1622	0.3533		-4	-2	0.3	44.04
c.1639T>C	C547R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C547R is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while no tool in the dataset predicts a benign outcome. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. Based on the unanimous computational evidence, the variant is most likely pathogenic, a conclusion that contradicts the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.007912	Uncertain	0.971	0.275	0.000					Uncertain		1				-16.967	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	7.76	Destabilizing	0.8	5.83	Destabilizing	6.80	Destabilizing	1.69	Destabilizing	0.900	Likely Pathogenic	-11.60	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.33	Pathogenic	0.02	Affected	3.37	35	0.1802	0.1408		-4	-3	-7.0	53.05	267.4	-90.3	0.0	0.0	-0.1	0.1	X	X	X				X	Potentially Pathogenic	Cys547 is located in an α-helix (res. Ala533-Val560). The thiol side chain of Cys is situated in a hydrophobic inter-helix space, where it packs hydrophobically with other residues such as Ile626, Leu551, and Phe652. Additionally, the thiol side chain of Cys547 weakly hydrogen bonds with the carbonyl group of Leu543 in the same α-helix. In the variant simulations, the bulkier, positively charged guanidinium group of Arg547 must rotate out of the hydrophobic space. Consequently, it forms ionic interactions with the carboxylate groups of Glu548 in the same helix and Glu656 in the neighboring α-helix (res. Glu666-Asp644). This causes the two helices to slightly separate, significantly affecting the secondary structure integrity of the latter helix. These negative structural effects could be more pronounced during protein folding and are likely to be undermined in the MD simulations.
c.1640G>A	C547Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C547Y (ClinVar ID 1404191.0) is listed as Pathogenic in ClinVar and is not reported in gnomAD. Prediction tools that agree on a benign effect include only SIFT, whereas the remaining tools—REVEL, FoldX, Rosetta, Foldetta, premPS (uncertain), PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. Taken together, the overwhelming majority of computational evidence indicates a pathogenic effect, which is in agreement with the ClinVar classification. Thus, the variant is most likely pathogenic and does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.007912	Uncertain	0.971	0.275	0.000					Pathogenic		1				-15.871	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	8.53	Destabilizing	1.8	6.20	Destabilizing	7.37	Destabilizing	0.62	Ambiguous	0.874	Likely Pathogenic	-10.57	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.33	Pathogenic	0.06	Tolerated	3.37	35	0.1393	0.2742		0	-2	-3.8	60.04	280.1	-54.8	0.0	0.0	0.0	0.0		X	X				X	Potentially Pathogenic	Cys547 is located in an α-helix (res. Ala533-Val560). The thiol side chain of Cys547 is situated in a hydrophobic inter-helix space, where it packs hydrophobically with other residues such as Ile626, Leu551, and Phe652. Additionally, the thiol side chain of Cys weakly hydrogen bonds with the carbonyl group of Leu543 in the same α-helix. In the variant simulations, the bulkier phenol ring of Tyr547, with its polar hydroxyl group, is less suited for the hydrophobic space. Consequently, it moves outside and forms a hydrogen bond with the carbonyl group of Phe652 in the neighboring α-helix (res. Glu666-Asp644). This causes the two helices to slightly separate, negatively affecting the secondary structure integrity of the latter helix. These negative structural effects could be more pronounced during protein folding and are likely to be undermined in the MD simulations.
c.1640G>T	C547F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C547F is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that assess the variant’s effect fall into two groups: the single benign prediction comes from premPS, while all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify it as pathogenic. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates pathogenicity, and Foldetta (combining FoldX‑MD and Rosetta outputs) reports a destabilizing, pathogenic effect. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions and the absence of any ClinVar annotation, the variant is most likely pathogenic, with no contradiction from ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.007912	Uncertain	0.971	0.275	0.000											-15.404	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	5.63	Destabilizing	1.2	5.82	Destabilizing	5.73	Destabilizing	0.49	Likely Benign	0.828	Likely Pathogenic	-10.57	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.29	Pathogenic	0.05	Affected			0.1603	0.3260		-4	-2	0.3	44.04
c.1652T>G	L551R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L551R is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a pathogenic effect include REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; the only tool with an uncertain outcome is FoldX. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. Based on the concordant predictions from multiple independent algorithms and the absence of benign evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009977	Structured	0.006653	Uncertain	0.960	0.254	0.000											-15.420	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.81	Ambiguous	0.2	2.35	Destabilizing	2.08	Destabilizing	2.09	Destabilizing	0.949	Likely Pathogenic	-3.85	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.60	Pathogenic	0.01	Affected			0.1278	0.0530		-3	-2	-8.3	43.03
c.1654T>C	C552R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C552R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only SIFT, whereas the remaining tools (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) yields an uncertain result, which is treated as unavailable evidence. Overall, the preponderance of predictions supports a pathogenic classification, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.013265	Structured	0.005714	Uncertain	0.955	0.256	0.000											-14.315	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	-1.18	Ambiguous	0.1	-0.51	Ambiguous	-0.85	Ambiguous	1.10	Destabilizing	0.809	Likely Pathogenic	-9.93	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.19	Pathogenic	0.48	Tolerated			0.1449	0.1366		-4	-3	-7.0	53.05
c.1655G>A	C552Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C552Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from premPS and SIFT, and pathogenic predictions from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results are reported by FoldX, Rosetta, and Foldetta. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic, while Foldetta’s stability analysis is inconclusive. Overall, the majority of evidence points to a pathogenic impact for C552Y. This conclusion is consistent with the absence of ClinVar annotation and does not contradict any existing database status. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.013265	Structured	0.005714	Uncertain	0.955	0.256	0.000											-13.195	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	-0.96	Ambiguous	0.1	-0.57	Ambiguous	-0.77	Ambiguous	0.41	Likely Benign	0.750	Likely Pathogenic	-9.37	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.23	Pathogenic	0.07	Tolerated			0.0988	0.2563		0	-2	-3.8	60.04
c.1655G>T	C552F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C552F is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include Rosetta, premPS, and SIFT, whereas the majority of tools predict it to be pathogenic: REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score. FoldX and Foldetta give uncertain results. High‑accuracy methods specifically report AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the consensus of the available predictions indicates that the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.013265	Structured	0.005714	Uncertain	0.955	0.256	0.000											-14.979	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	-1.01	Ambiguous	0.1	-0.35	Likely Benign	-0.68	Ambiguous	0.40	Likely Benign	0.759	Likely Pathogenic	-9.51	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.25	Pathogenic	0.07	Tolerated			0.1209	0.3081		-4	-2	0.3	44.04
c.1657A>G	K553E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K553E missense variant is not reported in ClinVar (status: None) and has no entries in gnomAD. Prediction tools that agree on a benign effect include only SIFT, whereas the remaining tools (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict pathogenicity. FoldX and Rosetta give uncertain results, and Foldetta also reports an uncertain stability change. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a deleterious effect. Thus, the variant is most likely pathogenic based on current predictions, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.012270	Structured	0.006539	Uncertain	0.949	0.246	0.000											-17.415	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.08	Ambiguous	0.3	1.15	Ambiguous	1.12	Ambiguous	1.04	Destabilizing	0.828	Likely Pathogenic	-3.85	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.35	Pathogenic	0.12	Tolerated			0.2890	0.0650		0	1	0.4	0.94
c.1666A>C	N556H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N556H is not reported in ClinVar and has no entries in gnomAD. Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, premPS, SIFT, and AlphaMissense‑Optimized. Tools that predict pathogenicity are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized labeling the variant as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicating likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicting benign stability. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict the absence of a ClinVar classification. Thus, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.015078	Structured	0.008655	Uncertain	0.925	0.225	0.000											-8.877	Likely Pathogenic	0.570	Likely Pathogenic	Likely Benign	0.33	Likely Benign	0.0	0.12	Likely Benign	0.23	Likely Benign	0.08	Likely Benign	0.744	Likely Pathogenic	-4.06	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.39	Pathogenic	0.10	Tolerated			0.1177	0.2940		2	1	0.3	23.04
c.1681T>G	F561V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F561V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Pathogenic. All available evidence points to a pathogenic impact. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.018013	Uncertain	0.903	0.196	0.000											-11.371	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	3.11	Destabilizing	0.1	2.58	Destabilizing	2.85	Destabilizing	1.48	Destabilizing	0.827	Likely Pathogenic	-6.97	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.25	Pathogenic	0.04	Affected			0.1985	0.1575		-1	-1	1.4	-48.04
c.1684C>A	P562T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P562T is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a pathogenic effect include SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign outcome; the only uncertain predictions come from Foldetta and premPS. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, while Foldetta remains uncertain. Taken together, the overwhelming majority of computational evidence indicates that P562T is likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.022306	Structured	0.023606	Uncertain	0.893	0.200	0.000											-14.747	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	2.62	Destabilizing	0.1	0.51	Ambiguous	1.57	Ambiguous	0.81	Ambiguous	0.697	Likely Pathogenic	-7.96	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.58	Pathogenic	0.00	Affected			0.1892	0.3454		0	-1	0.9	3.99
c.1688G>A	R563K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R563K missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Predictions that are inconclusive are Rosetta and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as Likely Benign, and Foldetta as benign. Based on the overall consensus of the available predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.039760	Structured	0.031987	Uncertain	0.876	0.209	0.000											-10.948	Likely Pathogenic	0.335	Likely Benign	Likely Benign	0.25	Likely Benign	0.0	0.66	Ambiguous	0.46	Likely Benign	0.70	Ambiguous	0.198	Likely Benign	-2.37	Neutral	0.990	Probably Damaging	0.998	Probably Damaging	3.46	Benign	0.35	Tolerated			0.4434	0.2379		3	2	0.6	-28.01
c.1688G>T	R563M 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R563M is reported in gnomAD (ID 6‑33440740‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, FATHMM, premPS, and Foldetta; pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (integrating FoldX‑MD and Rosetta outputs) as benign. No prediction or stability result is missing; all available data are considered. Overall, the balance of evidence leans toward a pathogenic effect, with a single high‑accuracy tool (Foldetta) suggesting benign stability. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.039760	Structured	0.031987	Uncertain	0.876	0.209	0.000								6-33440740-G-T			-8.910	Likely Pathogenic	0.934	Likely Pathogenic	Ambiguous	-0.18	Likely Benign	0.1	0.70	Ambiguous	0.26	Likely Benign	0.17	Likely Benign	0.311	Likely Benign	-4.91	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.43	Benign	0.04	Affected	3.37	35	0.1636	0.2230		-1	0	6.4	-24.99
c.1691A>C	E564A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E564A is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include premPS and SIFT, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results are reported by FoldX, Rosetta, and Foldetta. High‑accuracy assessments reinforce the pathogenic prediction: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence from multiple independent predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.023534	Structured	0.038418	Uncertain	0.891	0.208	0.000											-14.506	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic	0.64	Ambiguous	0.1	1.49	Ambiguous	1.07	Ambiguous	0.24	Likely Benign	0.765	Likely Pathogenic	-5.91	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.33	Pathogenic	0.12	Tolerated			0.3201	0.4918		0	-1	5.3	-58.04
c.1691A>G	E564G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E564G is listed in gnomAD (ID 6‑33440743‑A‑G) but has no ClinVar entry. Prediction tools that assess pathogenicity are unanimous: REVEL, FoldX (uncertain), Rosetta, Foldetta, premPS (uncertain), PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a pathogenic effect, while no tool predicts a benign outcome. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Thus, the variant is most likely pathogenic based on the available predictions, and this assessment is not contradicted by ClinVar status, which currently contains no entry for E564G. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.023534	Structured	0.038418	Uncertain	0.891	0.208	0.000								6-33440743-A-G			-15.053	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic	1.69	Ambiguous	0.1	2.55	Destabilizing	2.12	Destabilizing	0.80	Ambiguous	0.735	Likely Pathogenic	-6.83	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.23	Pathogenic	0.04	Affected	3.37	35	0.2749	0.4443		-2	0	3.1	-72.06
c.1694T>G	L565R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L565R is not reported in ClinVar (ClinVar status: not listed) but is present in the gnomAD database (gnomAD ID: 6‑33440746‑T‑G). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, Foldetta, and the SGM Consensus—consistently predict a pathogenic impact. The Rosetta stability assessment is inconclusive and is therefore treated as unavailable. High‑accuracy methods all support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar evidence (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.034884	Structured	0.045819	Uncertain	0.922	0.205	0.000								6-33440746-T-G			-16.070	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	4.71	Destabilizing	0.1	1.88	Ambiguous	3.30	Destabilizing	2.66	Destabilizing	0.547	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.74	Benign	0.00	Affected	3.37	35	0.1373	0.0615		-2	-3	-8.3	43.03
c.1696A>G	K566E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K566E missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Across the evaluated tools, every predictor that returned a definitive call classified the variant as pathogenic: SGM‑Consensus, REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool reported a benign outcome; the only inconclusive result was from Rosetta, which was labeled “Uncertain.” High‑accuracy assessments—AlphaMissense‑Optimized, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta—each returned a pathogenic prediction. Consequently, the variant is most likely pathogenic based on the consensus of predictive algorithms, and this assessment does not contradict any existing ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.027463	Structured	0.047887	Uncertain	0.924	0.219	0.000											-10.759	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	3.76	Destabilizing	0.2	1.13	Ambiguous	2.45	Destabilizing	1.58	Destabilizing	0.832	Likely Pathogenic	-3.58	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.38	Pathogenic	0.04	Affected			0.3275	0.0850		0	1	0.4	0.94
c.1703T>A	V568E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V568E is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity are unanimous: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool in the dataset predicts a benign effect, so the benign‑prediction group is empty. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized indicates pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a destabilizing, pathogenic effect. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.053503	Uncertain	0.937	0.257	0.000											-13.835	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	2.48	Destabilizing	0.1	4.62	Destabilizing	3.55	Destabilizing	2.03	Destabilizing	0.940	Likely Pathogenic	-5.88	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.46	Pathogenic	0.00	Affected			0.0891	0.1495		-2	-2	-7.7	29.98
c.1705T>G	F569V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F569V is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024393	Structured	0.054289	Uncertain	0.941	0.242	0.000											-14.248	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	4.74	Destabilizing	0.2	5.40	Destabilizing	5.07	Destabilizing	1.73	Destabilizing	0.874	Likely Pathogenic	-6.97	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.29	Pathogenic	0.00	Affected			0.2054	0.1422		-1	-1	1.4	-48.04
c.1708G>C	A570P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A570P is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity uniformly indicate a deleterious effect: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. No tool predicts a benign outcome. High‑accuracy methods corroborate this: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the unanimous pathogenic predictions and the absence of any benign calls, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which simply lacks an entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.046336	Structured	0.054494	Uncertain	0.932	0.263	0.000											-15.178	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	5.21	Destabilizing	0.5	8.45	Destabilizing	6.83	Destabilizing	1.19	Destabilizing	0.832	Likely Pathogenic	-4.55	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.31	Pathogenic	0.02	Affected			0.1965	0.2578		1	-1	-3.4	26.04
c.1709C>A	A570D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A570D is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect, so the benign group is empty. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Pathogenic. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.046336	Structured	0.054494	Uncertain	0.932	0.263	0.000											-14.117	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	2.47	Destabilizing	1.2	2.33	Destabilizing	2.40	Destabilizing	1.36	Destabilizing	0.805	Likely Pathogenic	-5.31	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.28	Pathogenic	0.03	Affected			0.2006	0.2206		0	-2	-5.3	44.01
c.1724G>A	R575H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R575H (ClinVar ID 1029088.0) is listed as Uncertain in ClinVar and is present in gnomAD (ID 6‑33440776‑G‑A). Prediction tools that indicate a benign effect include Rosetta, Foldetta, PROVEAN, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, Foldetta as Benign, and the SGM Consensus as Pathogenic. Overall, the majority of evidence points to a pathogenic impact, which contrasts with the ClinVar designation of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.061840	Structured	0.021362	Uncertain	0.916	0.259	0.000					Conflicting		4	6-33440776-G-A	204	1.27e-4	-11.142	Likely Pathogenic	0.496	Ambiguous	Likely Benign	0.81	Ambiguous	0.2	-0.22	Likely Benign	0.30	Likely Benign	1.31	Destabilizing	0.707	Likely Pathogenic	-2.34	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	-1.33	Pathogenic	0.05	Affected	3.37	35	0.2361	0.1292		2	0	1.3	-19.05	244.7	80.6	0.0	0.0	0.3	0.0		X						Potentially Pathogenic	The guanidinium group of Arg575, located in an α-helix (res. Arg563-Glu578), forms salt bridges with the carboxylate groups of Asp463 and Asp467, and it also hydrogen bonds with the hydroxyl group of Ser466 on an opposing α-helix (res. Ala461-Phe476) in the WT simulations. In the variant simulations, the imidazole ring of His575 (in its neutral epsilon protonated form) cannot form the same salt bridges as the guanidinium group of the non-mutated Arg575. Instead, His575 only forms weak hydrogen bonds with the hydroxyl groups of Ser466 and Ser571. Overall, the residue swap has the potential to substantially affect the tertiary structure assembly during the protein folding process.
c.1729G>C	A577P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A577P is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only SIFT, whereas the remaining evaluated algorithms (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict a pathogenic outcome; premPS is inconclusive and is therefore not counted. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Based on the consensus of these predictions, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.019074	Uncertain	0.913	0.239	0.000											-9.009	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	3.93	Destabilizing	0.2	9.88	Destabilizing	6.91	Destabilizing	0.87	Ambiguous	0.585	Likely Pathogenic	-2.72	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.34	Pathogenic	0.20	Tolerated			0.2256	0.4600		1	-1	-3.4	26.04
c.1733A>C	E578A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E578A missense change is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, and AlphaMissense‑Optimized; pathogenic predictions come from REVEL, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. ESM1b is uncertain. High‑accuracy assessment shows AlphaMissense‑Optimized predicts benign, while the SGM consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) favors pathogenic, and Foldetta also predicts benign. Overall, the majority of conventional tools lean benign, but the high‑accuracy consensus and AlphaMissense‑Optimized suggest a pathogenic effect. Thus, the variant is most likely pathogenic according to the most reliable predictors, and this assessment does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.059222	Structured	0.020971	Uncertain	0.902	0.240	0.000											-7.369	In-Between	0.604	Likely Pathogenic	Likely Benign	0.34	Likely Benign	0.1	-0.48	Likely Benign	-0.07	Likely Benign	-0.02	Likely Benign	0.525	Likely Pathogenic	-2.30	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	-1.40	Pathogenic	0.44	Tolerated			0.3326	0.5118		0	-1	5.3	-58.04
c.1733A>G	E578G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E578G missense change is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include premPS, PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are REVEL, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. Four tools give uncertain or inconclusive results (FoldX, Rosetta, Foldetta, ESM1b). High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—predicts pathogenic. Foldetta, a protein‑folding stability method, yields an uncertain result. Overall, the majority of high‑confidence predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.059222	Structured	0.020971	Uncertain	0.902	0.240	0.000											-7.680	In-Between	0.601	Likely Pathogenic	Likely Benign	0.98	Ambiguous	0.1	0.63	Ambiguous	0.81	Ambiguous	0.08	Likely Benign	0.589	Likely Pathogenic	-2.40	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	-1.49	Pathogenic	0.19	Tolerated			0.2608	0.4843		0	-2	3.1	-72.06
c.1754C>A	A585E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A585E is not reported in ClinVar (status: None) and is absent from gnomAD. Prediction tools cluster into two groups: the single benign call comes from SIFT, while all other evaluated algorithms—including REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—label the change as pathogenic or likely pathogenic. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports pathogenic. Thus, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.055884	Uncertain	0.880	0.244	0.000											-14.715	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	5.38	Destabilizing	0.7	3.70	Destabilizing	4.54	Destabilizing	1.42	Destabilizing	0.539	Likely Pathogenic	-2.59	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.30	Pathogenic	0.28	Tolerated			0.1160	0.1212		0	-1	-5.3	58.04
c.1763T>G	L588R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L588R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity uniformly classify the variant as pathogenic: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy methods corroborate this: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. All available evidence points to a deleterious impact. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.038042	Structured	0.082229	Uncertain	0.887	0.214	0.000											-15.602	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	6.96	Destabilizing	0.4	6.14	Destabilizing	6.55	Destabilizing	2.07	Destabilizing	0.942	Likely Pathogenic	-5.98	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.42	Pathogenic	0.00	Affected			0.1209	0.0530		-3	-2	-8.3	43.03
c.1778T>G	L593R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L593R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining 13 tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a destabilizing, pathogenic effect. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009728	Structured	0.110534	Uncertain	0.941	0.151	0.000											-16.139	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	4.27	Destabilizing	0.3	3.39	Destabilizing	3.83	Destabilizing	2.11	Destabilizing	0.740	Likely Pathogenic	-5.87	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.77	Benign	0.00	Affected			0.1440	0.0615		-3	-2	-8.3	43.03
c.1780T>G	F594V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F594V lies within the GAP domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that assess pathogenicity unanimously favor a deleterious effect: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity; only Rosetta is uncertain. No tool predicts a benign outcome. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta) is pathogenic. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which simply lacks an entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009187	Structured	0.120166	Uncertain	0.946	0.147	0.000											-12.648	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	2.91	Destabilizing	0.2	1.90	Ambiguous	2.41	Destabilizing	1.80	Destabilizing	0.931	Likely Pathogenic	-6.97	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.91	Pathogenic	0.01	Affected			0.1813	0.1575		-1	-1	1.4	-48.04
c.1784T>G	L595R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L595R is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include only FATHMM, while the majority of tools (SGM‑Consensus, REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; FoldX and Foldetta are uncertain. High‑accuracy methods give a pathogenic signal: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, and Foldetta remains uncertain. Overall, the evidence strongly favors a pathogenic effect, and this conclusion does not contradict any ClinVar annotation, as no ClinVar record exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.015344	Structured	0.128444	Uncertain	0.920	0.150	0.000											-14.601	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	1.22	Ambiguous	0.0	2.20	Destabilizing	1.71	Ambiguous	1.52	Destabilizing	0.707	Likely Pathogenic	-5.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.76	Benign	0.00	Affected			0.1344	0.1005		-3	-2	-8.3	43.03
c.1789T>G	F597V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F597V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect. Benign predictions: none. Pathogenic predictions: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. All available evidence points to a pathogenic effect. Therefore, the variant is most likely pathogenic, and this conclusion is consistent with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.010926	Structured	0.142961	Uncertain	0.944	0.151	0.000											-13.883	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic	3.75	Destabilizing	0.7	2.02	Destabilizing	2.89	Destabilizing	1.60	Destabilizing	0.939	Likely Pathogenic	-6.97	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-2.16	Pathogenic	0.01	Affected			0.2237	0.1583		-1	-1	1.4	-48.04
c.1795T>C	C599R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C599R is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a deleterious effect: REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, PROVEAN, ESM1b, FATHMM, premPS, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic, while FoldX reports an uncertain outcome. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic status; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009865	Structured	0.151725	Uncertain	0.960	0.151	0.000											-15.968	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.3	3.29	Destabilizing	2.15	Destabilizing	1.54	Destabilizing	0.909	Likely Pathogenic	-11.95	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.50	Pathogenic	0.00	Affected			0.1519	0.1566		-4	-3	-7.0	53.05
c.1796G>A	C599Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C599Y is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that indicate a benign effect include only premPS, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized reports pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming agreement among the majority of tools, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009865	Structured	0.151725	Uncertain	0.960	0.151	0.000											-13.563	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	4.00	Destabilizing	1.4	2.80	Destabilizing	3.40	Destabilizing	-0.29	Likely Benign	0.905	Likely Pathogenic	-10.95	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.49	Pathogenic	0.00	Affected			0.1092	0.2555		0	-2	-3.8	60.04
c.1796G>T	C599F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C599F is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that assess the variant’s effect largely agree on a deleterious outcome: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic or likely pathogenic. Only premPS predicts a benign effect. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized reports pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. No prediction or folding‑stability result is missing or inconclusive. Based on the overwhelming majority of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009865	Structured	0.151725	Uncertain	0.960	0.151	0.000											-13.969	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	3.72	Destabilizing	1.3	2.70	Destabilizing	3.21	Destabilizing	-0.42	Likely Benign	0.902	Likely Pathogenic	-10.95	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.47	Pathogenic	0.00	Affected			0.1319	0.3073		-4	-2	0.3	44.04
c.1798C>A	P600T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P600T is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include Foldetta, Rosetta, and premPS. Those that predict pathogenicity are REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus as likely pathogenic, while Foldetta indicates a benign effect on protein folding stability. Overall, the majority of computational evidence supports a pathogenic effect for P600T, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009728	Structured	0.162960	Uncertain	0.947	0.147	0.000											-11.945	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	2.61	Destabilizing	0.1	-2.90	Stabilizing	-0.15	Likely Benign	0.24	Likely Benign	0.737	Likely Pathogenic	-7.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.34	Pathogenic	0.01	Affected			0.1871	0.4954		0	-1	0.9	3.99
c.1801G>C	A601P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A601P is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, while the remaining 12 tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all classify it as pathogenic. The high‑accuracy methods—AlphaMissense‑Optimized, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta (combining FoldX‑MD and Rosetta outputs)—all report pathogenicity. No prediction or stability result is missing or inconclusive. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.008895	Structured	0.174517	Uncertain	0.955	0.156	0.000											-14.584	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	4.90	Destabilizing	0.6	8.84	Destabilizing	6.87	Destabilizing	0.87	Ambiguous	0.713	Likely Pathogenic	-4.98	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.56	Benign	0.01	Affected			0.2176	0.4328		1	-1	-3.4	26.04
c.1806T>G	I602M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I602M variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. In contrast, the majority of tools predict it to be pathogenic: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show a split: AlphaMissense‑Optimized and Foldetta both predict benign, whereas the SGM‑Consensus predicts pathogenic. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.010221	Structured	0.186541	Uncertain	0.963	0.171	0.000											-10.839	Likely Pathogenic	0.638	Likely Pathogenic	Likely Benign	0.03	Likely Benign	0.1	0.48	Likely Benign	0.26	Likely Benign	1.10	Destabilizing	0.675	Likely Pathogenic	-2.91	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.97	Pathogenic	0.00	Affected			0.0801	0.2321		2	1	-2.6	18.03
c.1813C>A	P605T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P605T is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a pathogenic effect include SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; no tool predicts a benign outcome. High‑accuracy methods specifically show pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No predictions or stability results are missing or inconclusive. Based on the unanimous pathogenic predictions and the absence of any ClinVar or gnomAD evidence to the contrary, the variant is most likely pathogenic and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.023087	Structured	0.192737	Uncertain	0.929	0.231	0.000											-11.533	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	2.87	Destabilizing	0.4	2.14	Destabilizing	2.51	Destabilizing	0.72	Ambiguous	0.801	Likely Pathogenic	-7.96	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.69	Pathogenic	0.00	Affected			0.1626	0.5228		0	-1	0.9	3.99
c.1817G>T	S606I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S606I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, Rosetta, Foldetta, premPS, and FATHMM, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; FoldX is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evidence points toward a pathogenic impact for S606I. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.191720	Uncertain	0.875	0.247	0.000											-14.552	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	-0.60	Ambiguous	0.1	-0.08	Likely Benign	-0.34	Likely Benign	0.41	Likely Benign	0.288	Likely Benign	-5.98	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	3.31	Benign	0.01	Affected			0.0891	0.4162		-1	-2	5.3	26.08
c.1820T>G	L607R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L607R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FoldX, which scores the variant as benign. All other evaluated algorithms—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic impact. Rosetta and Foldetta provide uncertain results and are therefore treated as unavailable evidence. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic,” while Foldetta remains uncertain. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.194229	Uncertain	0.869	0.250	0.000											-14.234	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	-0.15	Likely Benign	0.1	1.48	Ambiguous	0.67	Ambiguous	1.24	Destabilizing	0.920	Likely Pathogenic	-5.98	Deleterious	0.998	Probably Damaging	0.998	Probably Damaging	-1.51	Pathogenic	0.01	Affected			0.1490	0.0615		-3	-2	-8.3	43.03
c.1822T>G	F608V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F608V is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a pathogenic effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; all of these return a pathogenic or likely pathogenic label. No tool in the dataset predicts a benign outcome. Uncertain results are reported only for Rosetta and Foldetta, which are treated as unavailable evidence. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta remains uncertain. Taken together, the overwhelming majority of predictions indicate that F608V is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.106997	Structured	0.197190	Uncertain	0.891	0.247	0.000											-16.084	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	2.21	Destabilizing	0.1	1.39	Ambiguous	1.80	Ambiguous	1.47	Destabilizing	0.917	Likely Pathogenic	-6.97	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.59	Pathogenic	0.01	Affected			0.2193	0.2199		-1	-1	1.4	-48.04
c.1829T>G	L610R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L610R is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity are unanimous: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool in the dataset predicts a benign effect. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized reports a pathogenic outcome; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a pathogenic impact. Consequently, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.209504	Uncertain	0.888	0.253	0.000											-13.855	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	5.14	Destabilizing	0.5	4.60	Destabilizing	4.87	Destabilizing	1.89	Destabilizing	0.949	Likely Pathogenic	-5.94	Deleterious	0.998	Probably Damaging	0.998	Probably Damaging	-1.58	Pathogenic	0.00	Affected			0.1334	0.0615		-3	-2	-8.3	43.03
c.1838A>C	E613A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E613A missense variant is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include Rosetta, premPS, and Foldetta, whereas the majority of tools predict a pathogenic impact: REVEL, SIFT, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta stability outputs) as benign. Overall, the preponderance of evidence (10 pathogenic vs. 3 benign predictions) indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.275179	Structured	0.193489	Uncertain	0.816	0.254	0.000											-10.841	Likely Pathogenic	0.906	Likely Pathogenic	Ambiguous	0.90	Ambiguous	0.5	-0.17	Likely Benign	0.37	Likely Benign	0.32	Likely Benign	0.688	Likely Pathogenic	-5.57	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.26	Pathogenic	0.02	Affected			0.4696	0.5929		0	-1	5.3	-58.04
c.1838A>G	E613G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E613G is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include only premPS, whereas the remaining tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) uniformly predict a pathogenic impact. The high‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain. No prediction or stability assessment is missing or inconclusive beyond the uncertain labels. Overall, the preponderance of evidence points to a pathogenic effect for E613G, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.275179	Structured	0.193489	Uncertain	0.816	0.254	0.000											-12.417	Likely Pathogenic	0.911	Likely Pathogenic	Ambiguous	1.49	Ambiguous	0.3	1.34	Ambiguous	1.42	Ambiguous	0.08	Likely Benign	0.641	Likely Pathogenic	-6.56	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.26	Pathogenic	0.01	Affected			0.3422	0.5266		0	-2	3.1	-72.06
c.1843C>A	P615T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P615T is not reported in ClinVar and is absent from gnomAD. Among the evaluated in‑silico predictors, SIFT is the sole tool that predicts a benign effect, whereas the remaining majority—including REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic impact. Predictions from Rosetta, Foldetta, and premPS are uncertain and do not provide definitive evidence. High‑accuracy assessments further support a deleterious interpretation: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates it is likely pathogenic, while Foldetta’s stability analysis remains inconclusive. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.236433	Structured	0.179032	Uncertain	0.879	0.255	0.000											-13.764	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	3.02	Destabilizing	0.3	0.95	Ambiguous	1.99	Ambiguous	0.75	Ambiguous	0.823	Likely Pathogenic	-7.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.26	Pathogenic	0.06	Tolerated			0.1602	0.3806		0	-1	0.9	3.99
c.1850A>C	E617A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E617A is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include FoldX, premPS, SIFT, and AlphaMissense‑Optimized, whereas a majority of tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic outcome; Rosetta and Foldetta are uncertain. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized indicates benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates pathogenic, and Foldetta remains uncertain. Overall, the balance of evidence favors a pathogenic interpretation. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.155123	Uncertain	0.877	0.240	0.000											-8.704	Likely Pathogenic	0.769	Likely Pathogenic	Likely Benign	0.37	Likely Benign	0.1	0.89	Ambiguous	0.63	Ambiguous	0.18	Likely Benign	0.627	Likely Pathogenic	-4.75	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.37	Pathogenic	0.46	Tolerated			0.3033	0.5317		0	-1	5.3	-58.04
c.1850A>G	E617G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E617G is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from premPS, SIFT, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. Uncertain results are reported by FoldX, Rosetta, Foldetta, and ESM1b. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta is uncertain. Overall, the majority of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.155123	Uncertain	0.877	0.240	0.000											-7.984	In-Between	0.777	Likely Pathogenic	Likely Benign	0.59	Ambiguous	0.2	1.60	Ambiguous	1.10	Ambiguous	0.22	Likely Benign	0.701	Likely Pathogenic	-4.99	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.41	Pathogenic	0.18	Tolerated			0.2344	0.5442		0	-2	3.1	-72.06
c.1855A>T	T619S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T619S is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized. All other evaluated algorithms—SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments further support this view: AlphaMissense‑Optimized reports a benign outcome, whereas the SGM Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, yields an uncertain result. Overall, the majority of evidence points to a pathogenic effect for T619S, and this conclusion does not contradict the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.219301	Structured	0.119723	Uncertain	0.929	0.237	0.000					Uncertain		1				-8.608	Likely Pathogenic	0.677	Likely Pathogenic	Likely Benign	1.09	Ambiguous	0.2	1.35	Ambiguous	1.22	Ambiguous	0.85	Ambiguous	0.602	Likely Pathogenic	-3.42	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.30	Pathogenic	0.05	Affected	3.37	35	0.3255	0.2860		1	1	-0.1	-14.03
c.1856C>G	T619S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T619S missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized. All other evaluated predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) uniformly predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized remains benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, yields an uncertain result. No other high‑confidence stability predictions are available. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.219301	Structured	0.119723	Uncertain	0.929	0.237	0.000											-8.608	Likely Pathogenic	0.677	Likely Pathogenic	Likely Benign	1.09	Ambiguous	0.2	1.35	Ambiguous	1.22	Ambiguous	0.85	Ambiguous	0.523	Likely Pathogenic	-3.42	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.30	Pathogenic	0.05	Affected	3.37	35	0.3255	0.2860		1	1	-0.1	-14.03
c.1864A>T	T622S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T622S is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from SIFT and AlphaMissense‑Optimized, while pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized labeling the variant as benign, whereas the SGM‑Consensus predicts it to be likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result. No other folding‑stability tools provide conclusive evidence. Overall, the preponderance of predictions, including the SGM‑Consensus, indicates that T622S is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.071403	Uncertain	0.957	0.198	0.000											-9.840	Likely Pathogenic	0.669	Likely Pathogenic	Likely Benign	0.78	Ambiguous	0.1	1.36	Ambiguous	1.07	Ambiguous	0.80	Ambiguous	0.705	Likely Pathogenic	-3.52	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.50	Pathogenic	0.09	Tolerated			0.2523	0.3183		1	1	-0.1	-14.03
c.1865C>G	T622S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T622S is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from SIFT and AlphaMissense‑Optimized, while pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized labeling the variant as benign, whereas the SGM‑Consensus predicts it to be likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result. No other folding‑stability tools provide conclusive evidence. Overall, the preponderance of predictions, including the SGM‑Consensus, indicates that T622S is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.071403	Uncertain	0.957	0.198	0.000											-9.840	Likely Pathogenic	0.669	Likely Pathogenic	Likely Benign	0.78	Ambiguous	0.1	1.36	Ambiguous	1.07	Ambiguous	0.80	Ambiguous	0.595	Likely Pathogenic	-3.52	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.50	Pathogenic	0.09	Tolerated			0.2523	0.3183		1	1	-0.1	-14.03
c.1868T>G	L623R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L623R is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. All available evidence points to a pathogenic impact. Thus, the variant is most likely pathogenic, with no contradiction to ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.060667	Uncertain	0.962	0.211	0.000											-13.718	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	4.08	Destabilizing	1.4	3.28	Destabilizing	3.68	Destabilizing	2.31	Destabilizing	0.795	Likely Pathogenic	-5.98	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.55	Pathogenic	0.00	Affected			0.1327	0.0615		-3	-2	-8.3	43.03
c.1870A>C	T624P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T624P is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity uniformly indicate a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic, while premPS remains uncertain. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenic. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.137348	Structured	0.052894	Uncertain	0.962	0.217	0.000											-15.681	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic	3.64	Destabilizing	0.2	9.04	Destabilizing	6.34	Destabilizing	0.83	Ambiguous	0.914	Likely Pathogenic	-5.94	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.55	Pathogenic	0.01	Affected			0.1500	0.3569		0	-1	-0.9	-3.99
c.1874T>G	L625R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L625R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenic. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.229226	Structured	0.045896	Uncertain	0.966	0.215	0.000											-14.507	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	2.31	Destabilizing	0.7	4.21	Destabilizing	3.26	Destabilizing	1.88	Destabilizing	0.733	Likely Pathogenic	-5.93	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.99	Benign	0.00	Affected			0.1091	0.0615		-3	-2	-8.3	43.03
c.1882A>G	K628E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K628E missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a pathogenic effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that are inconclusive or uncertain are FoldX, Rosetta, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as Uncertain. Overall, the majority of evidence points to a deleterious effect. The variant is most likely pathogenic based on these predictions, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.088832	Structured	0.035486	Uncertain	0.957	0.229	0.000											-14.658	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	1.04	Ambiguous	0.2	0.52	Ambiguous	0.78	Ambiguous	1.06	Destabilizing	0.652	Likely Pathogenic	-3.98	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.37	Pathogenic	0.00	Affected			0.2909	0.0810		0	1	0.4	0.94
c.1885G>T	V629F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V629F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact; premPS is uncertain and is not counted as evidence. High‑accuracy methods further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta is pathogenic. No prediction is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions and the absence of any ClinVar annotation, the variant is most likely pathogenic, with no contradiction from ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.040537	Structured	0.034796	Uncertain	0.970	0.236	0.000											-13.484	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	3.41	Destabilizing	0.5	4.40	Destabilizing	3.91	Destabilizing	0.64	Ambiguous	0.642	Likely Pathogenic	-4.68	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.07	Benign	0.00	Affected			0.0560	0.2915		-1	-1	-1.4	48.04
c.1898T>G	L633R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L633R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. Based on the overwhelming consensus of pathogenic predictions and the absence of any benign signal, the variant is most likely pathogenic, and this conclusion does not contradict the current ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.045407	Uncertain	0.952	0.252	0.000											-14.360	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	4.41	Destabilizing	0.2	4.85	Destabilizing	4.63	Destabilizing	2.15	Destabilizing	0.667	Likely Pathogenic	-5.98	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.70	Benign	0.00	Affected			0.1674	0.0518		-3	-2	-8.3	43.03
c.1913A>C	K638T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K638T is not reported in ClinVar and is absent from gnomAD. Consensus from standard in silico predictors shows a split: benign calls come from REVEL, Rosetta, premPS, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default; FoldX and Foldetta are inconclusive. High‑accuracy assessments give AlphaMissense‑Optimized a benign score, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta remains uncertain. Overall, the balance of evidence favors a pathogenic effect for K638T. This prediction is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.098064	Uncertain	0.937	0.260	0.000											-8.856	Likely Pathogenic	0.775	Likely Pathogenic	Likely Benign	0.87	Ambiguous	0.0	0.23	Likely Benign	0.55	Ambiguous	0.07	Likely Benign	0.404	Likely Benign	-5.39	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	3.52	Benign	0.03	Affected			0.1632	0.2619		0	-1	3.2	-27.07
c.1913A>T	K638M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K638M missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include FoldX, FATHMM, premPS, and Foldetta. Those that predict a pathogenic effect comprise SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized and Rosetta give uncertain results, which are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of evidence points to a pathogenic impact, and this conclusion is not contradicted by the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.098064	Uncertain	0.937	0.260	0.000											-9.702	Likely Pathogenic	0.882	Likely Pathogenic	Ambiguous	-0.21	Likely Benign	0.0	0.61	Ambiguous	0.20	Likely Benign	0.09	Likely Benign	0.526	Likely Pathogenic	-5.19	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.41	Benign	0.01	Affected			0.0929	0.2896		0	-1	5.8	3.02
c.1943T>G	F648C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F648C is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools largely agree on a deleterious effect: all evaluated algorithms except FATHMM predict pathogenicity, while FATHMM alone predicts benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also reports a pathogenic effect. In summary, the overwhelming consensus from both general and high‑accuracy predictors is that F648C is pathogenic. This conclusion is consistent with the absence of any ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.051831	Structured	0.346782	Uncertain	0.943	0.339	0.000											-10.547	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	3.28	Destabilizing	0.1	3.35	Destabilizing	3.32	Destabilizing	1.22	Destabilizing	0.621	Likely Pathogenic	-7.98	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.40	Benign	0.03	Affected			0.2283	0.0783		-4	-2	-0.3	-44.04
c.1988T>G	F663C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F663C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.056825	Structured	0.093963	Uncertain	0.944	0.355	0.000											-13.544	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	3.83	Destabilizing	0.1	4.54	Destabilizing	4.19	Destabilizing	1.91	Destabilizing	0.772	Likely Pathogenic	-7.98	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.96	Benign	0.00	Affected			0.2343	0.0783		-4	-2	-0.3	-44.04
c.2075T>A	L692Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L692Q is listed in ClinVar as Pathogenic (ClinVar ID 2714634.0) and is not reported in gnomAD. Prediction tools that classify the variant as benign include only FATHMM. All other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic effect. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. No prediction or stability result is missing or inconclusive. Based on the consensus of these tools, the variant is most likely pathogenic, and this conclusion aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.064632	Structured	0.295225	Uncertain	0.966	0.243	0.000					Pathogenic		1				-13.873	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.24	Destabilizing	0.1	3.27	Destabilizing	3.26	Destabilizing	2.76	Destabilizing	0.596	Likely Pathogenic	-5.98	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.06	Benign	0.00	Affected	3.42	17	0.1079	0.0488		-2	-2	-7.3	14.97
c.2084T>C	L695P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L695P is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.118441	Structured	0.373419	Uncertain	0.942	0.258	0.000											-17.496	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	4.63	Destabilizing	0.2	4.73	Destabilizing	4.68	Destabilizing	2.11	Destabilizing	0.612	Likely Pathogenic	-6.85	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.16	Benign	0.00	Affected			0.3044	0.0992		-3	-3	-5.4	-16.04
c.2130G>C	K710N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K710N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, premPS, and FATHMM, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). Uncertain or unavailable results are reported for FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is inconclusive, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic impact for K710N, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.321458	Structured	0.370438	Uncertain	0.949	0.368	0.000											-9.330	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	0.85	Ambiguous	0.0	0.50	Ambiguous	0.68	Ambiguous	0.33	Likely Benign	0.201	Likely Benign	-4.39	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.04	Affected			0.2485	0.1124		1	0	0.4	-14.07
c.2130G>T	K710N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K710N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that indicate a benign effect include REVEL, premPS, and FATHMM. In contrast, a majority of algorithms predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the balance of evidence favors a pathogenic interpretation, and this conclusion does not conflict with the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.321458	Structured	0.370438	Uncertain	0.949	0.368	0.000											-9.330	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	0.85	Ambiguous	0.0	0.50	Ambiguous	0.68	Ambiguous	0.33	Likely Benign	0.201	Likely Benign	-4.39	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.04	Affected			0.2485	0.1124		1	0	0.4	-14.07
c.2134G>A	G712S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G712S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic impact comprise FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. Uncertain results come from premPS, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as pathogenic, and the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive and therefore unavailable. Overall, the majority of evidence points to a pathogenic effect for G712S. This conclusion does not contradict ClinVar, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.278302	Structured	0.384858	Uncertain	0.947	0.365	0.000											-7.942	In-Between	0.422	Ambiguous	Likely Benign	2.30	Destabilizing	0.1	4.79	Destabilizing	3.55	Destabilizing	0.62	Ambiguous	0.282	Likely Benign	-4.84	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.02	Affected			0.2862	0.4501		1	0	-0.4	30.03
c.2137C>T	P713S 2D AIThe SynGAP1 missense variant P713S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, Rosetta, and FATHMM, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). Uncertain results are provided by FoldX, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments further highlight this ambiguity: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus indicates a likely pathogenic effect, and Foldetta likewise yields an uncertain stability change. Overall, the majority of tools lean toward a pathogenic interpretation, and this aligns with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.393235	Uncertain	0.961	0.371	0.000											-8.496	Likely Pathogenic	0.846	Likely Pathogenic	Ambiguous	0.91	Ambiguous	0.7	0.19	Likely Benign	0.55	Ambiguous	0.62	Ambiguous	0.261	Likely Benign	-6.60	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.29	Benign	0.00	Affected			0.3234	0.3674		1	-1	0.8	-10.04
c.2138C>G	P713R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P713R has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and FATHMM. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The remaining tools, premPS and AlphaMissense‑Optimized, are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of predictions lean toward pathogenicity, while the most accurate methods give conflicting results. Thus, the variant is most likely pathogenic based on the current evidence, and this assessment does not contradict ClinVar status, which has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.393235	Uncertain	0.961	0.371	0.000											-12.101	Likely Pathogenic	0.930	Likely Pathogenic	Ambiguous	0.29	Likely Benign	0.0	0.21	Likely Benign	0.25	Likely Benign	0.86	Ambiguous	0.331	Likely Benign	-7.42	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.29	Benign	0.00	Affected			0.1366	0.2335		0	-2	-2.9	59.07
c.2138C>T	P713L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P713L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact; AlphaMissense‑Optimized and premPS are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the balance of evidence favors a pathogenic classification, and this conclusion does not contradict the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.393235	Uncertain	0.961	0.371	0.000											-11.323	Likely Pathogenic	0.850	Likely Pathogenic	Ambiguous	0.18	Likely Benign	0.1	-0.03	Likely Benign	0.08	Likely Benign	0.55	Ambiguous	0.324	Likely Benign	-8.60	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.34	Benign	0.00	Affected			0.1993	0.5261		-3	-3	5.4	16.04
c.2143C>T	P715S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P715S is listed in ClinVar as pathogenic (ClinVar ID 1804065.0) and is present in gnomAD (ID 6‑33441608‑C‑T). Functional prediction tools that agree on a benign effect are REVEL and FATHMM. Those that predict a pathogenic effect include FoldX, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. Predictions that are inconclusive are Rosetta, premPS, ESM1b, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of evidence points to a pathogenic impact, which is consistent with the ClinVar classification and does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.243554	Structured	0.409757	Uncertain	0.956	0.362	0.000					Likely Pathogenic		1	6-33441608-C-T	1	6.20e-7	-7.635	In-Between	0.787	Likely Pathogenic	Ambiguous	3.54	Destabilizing	0.0	0.81	Ambiguous	2.18	Destabilizing	0.94	Ambiguous	0.277	Likely Benign	-7.17	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.43	Benign	0.01	Affected	3.50	9	0.2977	0.3755		1	-1	0.8	-10.04	231.8	-14.0	-0.1	0.0	-0.8	0.1							X	Uncertain	Pro715, along with Gly712 and Pro713, are located in a hinge region of an α-helix making a ~90-degree turn (res. Lys705-Leu725). In the WT simulations, the pyrrolidine side chain of Pro715, lacking the backbone amide groups altogether, forces the tight helix turn to take place while also hydrophobically packing with nearby residues (e.g., Leu700, Leu708, Leu714, and Leu718). Leu715, with a normal amide backbone, could potentially affect protein folding and turn formation, although this was not observed in the variant simulations. Additionally, the hydroxyl group of the Ser715 side chain can form hydrogen bonds with the backbone carbonyl group of Gly712 and disrupt the hydrophobic packing arrangement of the leucine residues from the neighboring α-helices, impacting the GAP domain tertiary assembly.
c.2144C>A	P715H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P715H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas a majority of predictors (FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus) indicate a pathogenic impact. Tools with inconclusive results (Foldetta, premPS, AlphaMissense‑Optimized) are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the consensus of the majority of evidence points to a pathogenic effect for P715H. Based on the aggregate predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.243554	Structured	0.409757	Uncertain	0.956	0.362	0.000											-10.523	Likely Pathogenic	0.906	Likely Pathogenic	Ambiguous	2.80	Destabilizing	0.0	0.28	Likely Benign	1.54	Ambiguous	0.56	Ambiguous	0.271	Likely Benign	-7.73	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.37	Benign	0.00	Affected			0.1413	0.3684		0	-2	-1.6	40.02
c.2144C>G	P715R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P715R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors (SGM‑Consensus, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) classify the change as pathogenic. High‑accuracy assessments show that the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts a likely pathogenic outcome, AlphaMissense‑Optimized is inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. Because the pathogenic predictions outnumber the benign ones and the high‑accuracy consensus supports a deleterious effect, the variant is most likely pathogenic. This assessment does not contradict ClinVar, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.243554	Structured	0.409757	Uncertain	0.956	0.362	0.000											-12.191	Likely Pathogenic	0.940	Likely Pathogenic	Ambiguous	2.19	Destabilizing	0.1	0.53	Ambiguous	1.36	Ambiguous	0.87	Ambiguous	0.324	Likely Benign	-8.09	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.53	Benign	0.01	Affected			0.1389	0.2620		0	-2	-2.9	59.07
c.2144C>T	P715L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P715L is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL, Rosetta, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. FoldX and premPS give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as uncertain. Because the majority of consensus and individual predictors indicate pathogenicity, the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar, which contains no entry for P715L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.243554	Structured	0.409757	Uncertain	0.956	0.362	0.000											-12.207	Likely Pathogenic	0.764	Likely Pathogenic	Likely Benign	1.43	Ambiguous	0.1	0.06	Likely Benign	0.75	Ambiguous	0.58	Ambiguous	0.318	Likely Benign	-9.10	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.39	Benign	0.01	Affected			0.1944	0.5105		-3	-3	5.4	16.04
c.2153T>G	L718R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L718R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.298791	Structured	0.438417	Uncertain	0.966	0.385	0.000											-16.119	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	5.90	Destabilizing	0.2	5.05	Destabilizing	5.48	Destabilizing	2.57	Destabilizing	0.484	Likely Benign	-5.69	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.28	Pathogenic	0.00	Affected			0.1254	0.0600		-3	-2	-8.3	43.03
c.2157C>A	N719K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N719K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The remaining tools (FoldX, Rosetta, ESM1b, and Foldetta) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as uncertain. Overall, the majority of reliable predictions indicate a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.384043	Structured	0.445381	Uncertain	0.961	0.386	0.000											-7.454	In-Between	0.651	Likely Pathogenic	Likely Benign	-0.64	Ambiguous	0.0	-0.62	Ambiguous	-0.63	Ambiguous	0.42	Likely Benign	0.250	Likely Benign	-1.84	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.80	Benign	0.55	Tolerated			0.1424	0.3112		1	0	-0.4	14.07
c.2157C>G	N719K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N719K is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in silico predictors shows a predominance of benign calls: REVEL, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized all predict a neutral effect, whereas polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default predict pathogenicity. FoldX, Rosetta, ESM1b, and Foldetta are inconclusive. High‑accuracy assessment further supports a benign interpretation: AlphaMissense‑Optimized is benign; the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also yields a benign outcome; Foldetta remains uncertain. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.384043	Structured	0.445381	Uncertain	0.961	0.386	0.000											-7.454	In-Between	0.651	Likely Pathogenic	Likely Benign	-0.64	Ambiguous	0.0	-0.62	Ambiguous	-0.63	Ambiguous	0.42	Likely Benign	0.244	Likely Benign	-1.84	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.80	Benign	0.55	Tolerated			0.1424	0.3112		1	0	-0.4	14.07
c.2170G>C	A724P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A724P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: REVEL predicts a benign effect, whereas the remaining 13 tools (FoldX, Rosetta, Foldetta, premPS [uncertain], PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized returns a pathogenic score; the SGM Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, classifies the variant as pathogenic. No tool suggests a benign outcome, and the single benign prediction (REVEL) is outweighed by the consensus of pathogenic predictions. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this mutation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.476583	Structured	0.458050	Uncertain	0.923	0.483	0.250											-12.817	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	2.90	Destabilizing	0.3	6.35	Destabilizing	4.63	Destabilizing	0.52	Ambiguous	0.391	Likely Benign	-3.88	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.04	Pathogenic	0.04	Affected			0.1642	0.4273		1	-1	-3.4	26.04
c.2171C>A	A724D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A724D is not reported in ClinVar or gnomAD. Prediction tools that indicate a benign effect include REVEL, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact. Four methods (FoldX, Rosetta, Foldetta, premPS) returned uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic; Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for A724D, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.476583	Structured	0.458050	Uncertain	0.923	0.483	0.250											-12.233	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	1.06	Ambiguous	0.2	0.86	Ambiguous	0.96	Ambiguous	0.60	Ambiguous	0.335	Likely Benign	-4.44	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.03	Pathogenic	0.00	Affected			0.1596	0.1812		0	-2	-5.3	44.01
c.2174T>G	L725R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L725R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, AlphaMissense‑Optimized, premPS, Rosetta, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—classify the variant as pathogenic. FoldX and Foldetta report uncertain results and are therefore not considered evidence for either side. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus indicates likely pathogenic, while Foldetta remains uncertain. Based on the overwhelming majority of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, which is consistent with the absence of a ClinVar entry and gnomAD observation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.455613	Uncertain	0.911	0.491	0.625											-15.383	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic	0.69	Ambiguous	0.3	2.16	Destabilizing	1.43	Ambiguous	1.49	Destabilizing	0.345	Likely Benign	-5.46	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.28	Pathogenic	0.00	Affected			0.1374	0.0846		-3	-2	-8.3	43.03
c.2177G>A	R726K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R726K is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only two tools—polyPhen‑2 HumDiv and polyPhen‑2 HumVar—predict a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Benign”; and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. No prediction or folding‑stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.521092	Disordered	0.449098	Uncertain	0.888	0.513	0.625											-5.344	Likely Benign	0.231	Likely Benign	Likely Benign	0.28	Likely Benign	0.0	-0.02	Likely Benign	0.13	Likely Benign	0.20	Likely Benign	0.154	Likely Benign	-0.63	Neutral	0.990	Probably Damaging	0.998	Probably Damaging	2.67	Benign	0.16	Tolerated			0.4920	0.4042		3	2	0.6	-28.01
c.2177G>T	R726M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R726M has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, Foldetta, premPS, PROVEAN, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. FoldX is uncertain and is not counted as evidence. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, the majority of tools and the two high‑accuracy methods predict a benign effect. Therefore, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.521092	Disordered	0.449098	Uncertain	0.888	0.513	0.625											-8.611	Likely Pathogenic	0.750	Likely Pathogenic	Likely Benign	0.53	Ambiguous	0.1	0.31	Likely Benign	0.42	Likely Benign	0.20	Likely Benign	0.199	Likely Benign	-2.02	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.59	Benign	0.03	Affected			0.1489	0.4051		0	-1	6.4	-24.99
c.2179A>T	N727Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N727Y has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, premPS, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Two tools remain inconclusive: AlphaMissense‑Default and Rosetta. Separately, the high‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign. Overall, the majority of individual predictors and the SGM Consensus lean toward a pathogenic interpretation, while the high‑accuracy folding‑stability assessment is benign. Thus, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.442107	Uncertain	0.843	0.542	0.625											-10.106	Likely Pathogenic	0.426	Ambiguous	Likely Benign	-0.12	Likely Benign	0.1	-0.52	Ambiguous	-0.32	Likely Benign	0.35	Likely Benign	0.347	Likely Benign	-5.34	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.12	Pathogenic	0.02	Affected			0.0563	0.6091		-2	-2	2.2	49.07
c.2180A>T	N727I 2D 3DClick to see structure in 3D Viewer AISynGAP1 N727I is not reported in ClinVar and is absent from gnomAD. Benign predictions come from REVEL, FoldX, premPS, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen2_HumDiv, polyPhen2_HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Foldetta and Rosetta provide inconclusive results. High‑accuracy tools give a mixed picture: AlphaMissense‑Optimized predicts benign, SGM‑Consensus predicts likely pathogenic, and Foldetta is uncertain. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.442107	Uncertain	0.843	0.542	0.625											-10.230	Likely Pathogenic	0.577	Likely Pathogenic	Likely Benign	0.17	Likely Benign	0.1	0.90	Ambiguous	0.54	Ambiguous	0.43	Likely Benign	0.319	Likely Benign	-5.93	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.13	Pathogenic	0.03	Affected			0.0666	0.5917		-2	-3	8.0	-0.94
c.2182C>T	P728S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P728S is not reported in ClinVar and is present in gnomAD (ID 6‑33441647‑C‑T). Functional prediction tools that agree on a benign effect include REVEL, whereas the majority of tools predict pathogenicity: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain results from FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized are treated as unavailable. High‑accuracy consensus methods give a Likely Pathogenic verdict from the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and an Uncertain outcome from AlphaMissense‑Optimized; Foldetta also reports Uncertain. Overall, the preponderance of evidence points to a pathogenic effect for P728S, and this assessment does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.632174	Disordered	0.434760	Uncertain	0.725	0.567	0.625								6-33441647-C-T	1	6.20e-7	-9.047	Likely Pathogenic	0.897	Likely Pathogenic	Ambiguous	0.89	Ambiguous	0.0	0.98	Ambiguous	0.94	Ambiguous	0.54	Ambiguous	0.280	Likely Benign	-6.38	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.68	Pathogenic	0.00	Affected	3.59	7	0.3571	0.3571		-1	1	0.8	-10.04
c.2183C>A	P728H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P728H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default, all of which predict a deleterious impact. Predictions that are inconclusive or uncertain are FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. Overall, the majority of evidence points to a pathogenic effect for P728H, and this conclusion does not contradict any ClinVar status because the variant is not yet classified in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.632174	Disordered	0.434760	Uncertain	0.725	0.567	0.625											-8.897	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous	0.94	Ambiguous	0.0	0.86	Ambiguous	0.90	Ambiguous	0.64	Ambiguous	0.402	Likely Benign	-7.23	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.65	Pathogenic	0.00	Affected			0.1993	0.3016		0	-2	-1.6	40.02
c.2183C>G	P728R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P728R has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and FoldX, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain or inconclusive results are reported by Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments further indicate a likely pathogenic status from the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) and an uncertain outcome from Foldetta (combining FoldX‑MD and Rosetta). AlphaMissense‑Optimized also remains uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.632174	Disordered	0.434760	Uncertain	0.725	0.567	0.625											-10.309	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	0.45	Likely Benign	0.1	0.59	Ambiguous	0.52	Ambiguous	0.70	Ambiguous	0.418	Likely Benign	-7.46	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.66	Pathogenic	0.00	Affected			0.1728	0.2865		0	-2	-2.9	59.07
c.2183C>T	P728L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P728L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, and premPS, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact; FoldX and AlphaMissense‑Optimized are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the preponderance of evidence from standard and high‑accuracy predictors points to a pathogenic effect for P728L. This conclusion is not contradicted by any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.632174	Disordered	0.434760	Uncertain	0.725	0.567	0.625											-11.125	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	0.79	Ambiguous	0.0	0.15	Likely Benign	0.47	Likely Benign	0.20	Likely Benign	0.402	Likely Benign	-8.27	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.66	Pathogenic	0.00	Affected			0.2321	0.4713		-3	-3	5.4	16.04
c.2233C>G	P745A 2D AIThe SynGAP1 missense variant P745A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact for P745A, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.791621	Disordered	0.558331	Binding	0.341	0.860	0.875											-4.599	Likely Benign	0.057	Likely Benign	Likely Benign										0.171	Likely Benign	-2.88	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.55	Benign	0.17	Tolerated			0.3424	0.3458		1	-1	3.4	-26.04
c.2245C>T	R749W 2D AIThe SynGAP1 missense variant R749W is listed in ClinVar as benign and is observed in gnomAD (ID 6‑33441710‑C‑T). Prediction tools that classify the variant as benign include REVEL, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also returns benign, and Foldetta stability analysis is unavailable. Overall, the majority of evidence, especially from high‑confidence methods, supports a benign effect. This consensus aligns with the ClinVar designation, so there is no contradiction between the predictions and the reported clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.675549	Disordered	0.626050	Binding	0.337	0.860	0.625					Likely Benign		1	6-33441710-C-T	3	1.86e-6	-7.647	In-Between	0.338	Likely Benign	Likely Benign										0.173	Likely Benign	-2.62	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.59	Benign	0.00	Affected	4.32	2	0.1215	0.4088		2	-3	3.6	30.03
c.2326G>C	G776R 2D AIThe SynGAP1 missense variant G776R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which collectively suggest a likely benign outcome. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the Foldetta protein‑folding stability assessment is unavailable for this variant. Overall, the balance of evidence leans toward a benign interpretation, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.377384	Structured	0.886983	Binding	0.296	0.888	0.250											-6.209	Likely Benign	0.886	Likely Pathogenic	Ambiguous										0.181	Likely Benign	-2.28	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	4.22	Benign	0.01	Affected			0.0932	0.5115		-3	-2	-4.1	99.14
c.2326G>T	G776C 2D AIThe SynGAP1 missense variant G776C is not reported in ClinVar but is present in gnomAD (ID 6‑33442484‑G‑T). Prediction tools cluster into benign (REVEL, FATHMM, AlphaMissense‑Optimized) and pathogenic (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT). Two tools (ESM1b, AlphaMissense‑Default) return uncertain results. High‑accuracy assessments are limited: AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta data are unavailable. Overall, the majority of conventional predictors indicate pathogenicity, whereas the single high‑accuracy tool suggests benign. Given the preponderance of pathogenic predictions and the absence of a ClinVar entry, the variant is most likely pathogenic and does not contradict any existing ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.377384	Structured	0.886983	Binding	0.296	0.888	0.250								6-33442484-G-T			-7.974	In-Between	0.380	Ambiguous	Likely Benign										0.181	Likely Benign	-2.59	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	4.15	Benign	0.01	Affected	3.64	6	0.1235	0.4403		-3	-3	2.9	46.09
c.2327G>T	G776V 2D AIThe SynGAP1 missense variant G776V is listed in gnomAD (ID 6‑33442485‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar) and SIFT. AlphaMissense‑Default is uncertain, and Foldetta (FoldX‑MD/Rosetta stability assessment) has no result for this variant. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also indicates a likely benign outcome; Foldetta data are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar status because none is reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.377384	Structured	0.886983	Binding	0.296	0.888	0.250								6-33442485-G-T			-6.541	Likely Benign	0.515	Ambiguous	Likely Benign										0.180	Likely Benign	-2.25	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	4.19	Benign	0.01	Affected	3.64	6	0.0993	0.4223		-3	-1	4.6	42.08
c.2356C>T	L786F 2D AIThe SynGAP1 missense variant L786F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; Foldetta results are unavailable. Overall, the balance of evidence leans toward pathogenicity, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.882776	Disordered	0.655253	Binding	0.341	0.895	0.750											-4.949	Likely Benign	0.578	Likely Pathogenic	Likely Benign										0.112	Likely Benign	-2.53	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.83	Pathogenic	0.00	Affected			0.0765	0.3847		2	0	-1.0	34.02
c.2357T>G	L786R 2D AIThe SynGAP1 missense variant L786R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. The high‑accuracy consensus from SGM (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) favors pathogenicity, and the lack of a Foldetta result does not alter this conclusion. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant has not yet been catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.882776	Disordered	0.655253	Binding	0.341	0.895	0.750											-4.989	Likely Benign	0.842	Likely Pathogenic	Ambiguous										0.169	Likely Benign	-3.07	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.79	Pathogenic	0.00	Affected			0.1403	0.1288		-3	-2	-8.3	43.03
c.2359C>G	P787A 2D AIThe SynGAP1 P787A missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas a majority (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM) predict a pathogenic impact. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta results are unavailable. Overall, the balance of evidence—five pathogenic versus three benign predictions, with the SGM Consensus supporting pathogenicity—suggests that the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.901269	Disordered	0.613211	Binding	0.377	0.899	0.750											-4.542	Likely Benign	0.451	Ambiguous	Likely Benign										0.242	Likely Benign	-4.23	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.48	Pathogenic	0.02	Affected			0.3425	0.4444		1	-1	3.4	-26.04
c.2365C>G	P789A 2D AIThe SynGAP1 P789A missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a tie (2 benign, 2 pathogenic) and is therefore inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus remains inconclusive and Foldetta data are unavailable. Overall, the majority of tools (five out of nine) predict pathogenicity, but the presence of four benign predictions and the inconclusive high‑accuracy results suggest uncertainty. The variant is most likely pathogenic based on the current predictions, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.963420	Disordered	0.541575	Binding	0.398	0.903	0.750											-4.777	Likely Benign	0.235	Likely Benign	Likely Benign										0.258	Likely Benign	-4.92	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.11	Pathogenic	0.00	Affected			0.3120	0.3052		1	-1	3.4	-26.04
c.2417T>G	F806C 2D AIThe SynGAP1 missense variant F806C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict a pathogenic impact, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while SGM‑Consensus remains likely pathogenic; Foldetta results are unavailable. Based on the predominance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.736850	Disordered	0.847454	Binding	0.276	0.904	0.500											-8.565	Likely Pathogenic	0.809	Likely Pathogenic	Ambiguous										0.266	Likely Benign	-4.46	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.11	Pathogenic	0.00	Affected			0.3071	0.1125		-4	-2	-0.3	-44.04
c.2443C>T	R815C 2D AIThe SynGAP1 missense variant R815C is listed in ClinVar (ID 660618.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33442995‑C‑T). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized result is “Uncertain.” The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of predictions indicates a pathogenic effect, which does not contradict the ClinVar “Uncertain” classification but suggests that the variant is more likely pathogenic rather than benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.394753	Structured	0.780568	Binding	0.278	0.907	0.250					Uncertain		1	6-33442995-C-T	5	3.10e-6	-9.373	Likely Pathogenic	0.828	Likely Pathogenic	Ambiguous										0.174	Likely Benign	-3.89	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.59	Benign	0.00	Affected	4.32	4	0.3389	0.3682		-4	-3	7.0	-53.05
c.2444G>A	R815H 2D AIThe SynGAP1 missense variant R815H (ClinVar ID 833773.0) is classified as benign in ClinVar and is present in gnomAD (6‑33442996‑G‑A). Functional prediction tools cluster into two groups: benign predictions from REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions from polyPhen‑2 (HumDiv and HumVar) and SIFT. Two tools report uncertainty: ESM1b and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta stability assessment are unavailable. Overall, the balance of evidence favors a benign effect, consistent with the ClinVar annotation and with no conflict regarding its status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.394753	Structured	0.780568	Binding	0.278	0.907	0.250					Likely Benign		2	6-33442996-G-A	24	1.49e-5	-7.474	In-Between	0.553	Ambiguous	Likely Benign										0.157	Likely Benign	-1.81	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.61	Benign	0.02	Affected	4.32	4	0.2944	0.2281		2	0	1.3	-19.05																10.1016/j.ajhg.2020.11.011
c.2461T>C	C821R 2D AIThe SynGAP1 missense variant C821R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑accuracy predictors (six out of nine) indicate a pathogenic impact, while three suggest benign. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.745909	Disordered	0.672821	Binding	0.351	0.883	0.750											-3.997	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.183	Likely Benign	-2.93	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.69	Benign	0.03	Affected			0.1944	0.1746		-4	-3	-7.0	53.05
c.2462G>A	C821Y 2D AIThe SynGAP1 missense variant C821Y is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, seven tools support pathogenicity while three support benignity, and no high‑accuracy consensus contradicts this trend. Therefore, the variant is most likely pathogenic based on the available predictions, and this assessment does not conflict with the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.745909	Disordered	0.672821	Binding	0.351	0.883	0.750											-1.007	Likely Benign	0.982	Likely Pathogenic	Likely Pathogenic										0.342	Likely Benign	-3.11	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.66	Benign	0.01	Affected			0.1288	0.3187		0	-2	-3.8	60.04
c.2462G>T	C821F 2D AIThe SynGAP1 missense variant C821F is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default) predict a pathogenic impact; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, the balance of evidence favors a pathogenic classification, and this assessment does not contradict any existing ClinVar status because the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.745909	Disordered	0.672821	Binding	0.351	0.883	0.750											0.971	Likely Benign	0.924	Likely Pathogenic	Ambiguous										0.338	Likely Benign	-3.33	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.66	Benign	0.01	Affected			0.1504	0.3505		-4	-2	0.3	44.04
c.2463C>G	C821W 2D AIThe SynGAP1 missense variant C821W is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evaluated predictors (six pathogenic vs three benign) indicate a pathogenic impact. This prediction is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.745909	Disordered	0.672821	Binding	0.351	0.883	0.750											-4.843	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.201	Likely Benign	-3.30	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.64	Benign	0.01	Affected			0.1742	0.3268		-8	-2	-3.4	83.07
c.2467A>T	S823C 2D AIThe SynGAP1 missense variant S823C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. Two tools give uncertain results: ESM1b and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic, while AlphaMissense‑Optimized remains uncertain. No Foldetta stability prediction is available, so it does not contribute to the assessment. Overall, the preponderance of evidence points to a pathogenic effect for S823C, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-7.881	In-Between	0.911	Likely Pathogenic	Ambiguous										0.332	Likely Benign	-3.80	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.91	Pathogenic	0.00	Affected			0.1019	0.6137		0	-1	3.3	16.06
c.2468G>T	S823I 2D AIThe SynGAP1 missense variant S823I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only REVEL predicts a benign outcome, while ESM1b remains uncertain. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-7.332	In-Between	0.990	Likely Pathogenic	Likely Pathogenic										0.287	Likely Benign	-4.26	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.92	Pathogenic	0.00	Affected			0.0964	0.5848		-1	-2	5.3	26.08
c.2470A>T	S824C 2D AIThe SynGAP1 missense variant S824C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for S824C, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.611272	Binding	0.314	0.884	0.750											-6.613	Likely Benign	0.730	Likely Pathogenic	Likely Benign										0.108	Likely Benign	-1.87	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.57	Benign	0.07	Tolerated			0.1363	0.6277		0	-1	3.3	16.06
c.2471G>T	S824I 2D AIThe SynGAP1 missense variant S824I has no ClinVar record and is not listed in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign, reflecting the majority of benign calls. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and Foldetta results are unavailable. Overall, the balance of evidence—five benign versus three pathogenic calls, a benign SGM‑Consensus, and no conflicting ClinVar annotation—suggests that the variant is most likely benign. This conclusion does not contradict any existing ClinVar status, as none is present. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.611272	Binding	0.314	0.884	0.750											-6.799	Likely Benign	0.950	Likely Pathogenic	Ambiguous										0.124	Likely Benign	-1.18	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.60	Benign	0.11	Tolerated			0.1177	0.6045		-1	-2	5.3	26.08
c.2477A>C	D826A 2D AIThe SynGAP1 D826A missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evaluated predictors (six pathogenic vs. three benign) indicate a pathogenic impact. This prediction is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.666105	Disordered	0.627309	Binding	0.327	0.886	0.625											-5.590	Likely Benign	0.984	Likely Pathogenic	Likely Pathogenic										0.307	Likely Benign	-3.77	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.53	Benign	0.02	Affected			0.4463	0.7867		0	-2	5.3	-44.01
c.2480T>A	I827N 2D AIThe SynGAP1 missense variant I827N is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, whereas the SGM‑Consensus (majority vote) supports a benign prediction. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the preponderance of evidence points to a benign effect; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.590140	Disordered	0.636272	Binding	0.383	0.884	0.625											-4.860	Likely Benign	0.804	Likely Pathogenic	Ambiguous										0.114	Likely Benign	-1.69	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.66	Benign	0.11	Tolerated			0.0876	0.0342		-2	-3	-8.0	0.94
c.2481C>G	I827M 2D AIThe SynGAP1 missense variant I827M is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also likely benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.590140	Disordered	0.636272	Binding	0.383	0.884	0.625											-4.910	Likely Benign	0.282	Likely Benign	Likely Benign										0.143	Likely Benign	-0.61	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.65	Benign	0.13	Tolerated			0.0642	0.2560		2	1	-2.6	18.03
c.2482A>C	T828P 2D AIThe SynGAP1 missense variant T828P is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain. The SGM Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to benign (2 benign vs. 1 pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus as benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) is unavailable. Overall, the preponderance of evidence points to a benign impact for T828P, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.604312	Disordered	0.631236	Binding	0.321	0.879	0.500											-3.902	Likely Benign	0.466	Ambiguous	Likely Benign										0.280	Likely Benign	-2.53	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.61	Benign	0.12	Tolerated			0.1898	0.4424		0	-1	-0.9	-3.99
c.2483C>A	T828K 2D AIThe SynGAP1 missense variant T828K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, while the SGM‑Consensus (majority vote) remains Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.604312	Disordered	0.631236	Binding	0.321	0.879	0.500											-5.466	Likely Benign	0.853	Likely Pathogenic	Ambiguous										0.155	Likely Benign	-0.88	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.68	Benign	0.39	Tolerated			0.0924	0.2886		0	-1	-3.2	27.07
c.2483C>T	T828I 2D AISynGAP1 missense variant T828I is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, and FATHMM, whereas tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is a 2‑to‑2 split and therefore unavailable; Foldetta predictions are not provided. Consequently, the computational evidence is evenly divided between benign and pathogenic, with no clear direction. The variant is therefore not clearly benign or pathogenic based on current predictions, and this lack of consensus does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.604312	Disordered	0.631236	Binding	0.321	0.879	0.500											-4.971	Likely Benign	0.893	Likely Pathogenic	Ambiguous										0.139	Likely Benign	-3.40	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.61	Benign	0.06	Tolerated			0.0767	0.5262		0	-1	5.2	12.05
c.2488C>G	P830A 2D AIThe SynGAP1 missense variant P830A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus likewise indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar status, which contains no entry for P830A. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.590140	Disordered	0.618152	Binding	0.333	0.874	0.500											-4.471	Likely Benign	0.146	Likely Benign	Likely Benign										0.202	Likely Benign	-3.63	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.82	Benign	0.04	Affected			0.3534	0.5050		1	-1	3.4	-26.04
c.2509G>T	V837F 2D AIThe SynGAP1 missense variant V837F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.626284	Binding	0.318	0.871	0.125											-5.223	Likely Benign	0.322	Likely Benign	Likely Benign										0.164	Likely Benign	-1.41	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.60	Benign	0.08	Tolerated			0.0749	0.3744		-1	-1	-1.4	48.04
c.2510T>A	V837D 2D AIThe SynGAP1 missense variant V837D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign (three benign votes versus one pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.626284	Binding	0.318	0.871	0.125											-5.712	Likely Benign	0.785	Likely Pathogenic	Ambiguous										0.127	Likely Benign	-0.51	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.61	Benign	0.85	Tolerated			0.1415	0.0902		-2	-3	-7.7	15.96
c.2512A>C	N838H 2D AIThe SynGAP1 missense variant N838H is reported in ClinVar as “Not submitted” and is not present in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for the variant, and this conclusion does not contradict the ClinVar status, which currently contains no pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.622677	Disordered	0.613320	Binding	0.276	0.861	0.250											-6.650	Likely Benign	0.285	Likely Benign	Likely Benign										0.139	Likely Benign	-2.56	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.63	Benign	0.09	Tolerated			0.1417	0.5303		2	1	0.3	23.04
c.2512A>T	N838Y 2D AIThe SynGAP1 missense variant N838Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, while the SGM‑Consensus remains Likely Pathogenic; Foldetta results are unavailable. Overall, the majority of predictions (six pathogenic versus three benign) and the SGM‑Consensus lean toward a pathogenic interpretation. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.622677	Disordered	0.613320	Binding	0.276	0.861	0.250											-9.020	Likely Pathogenic	0.722	Likely Pathogenic	Likely Benign										0.266	Likely Benign	-4.09	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.62	Benign	0.05	Affected			0.0621	0.4258		-2	-2	2.2	49.07
c.2513A>T	N838I 2D AIThe SynGAP1 missense variant N838I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL and FATHMM, whereas a majority of algorithms predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for N838I. This conclusion is consistent with the absence of a ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.622677	Disordered	0.613320	Binding	0.276	0.861	0.250											-8.061	Likely Pathogenic	0.890	Likely Pathogenic	Ambiguous										0.170	Likely Benign	-4.44	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.63	Benign	0.01	Affected			0.0642	0.4900		-2	-3	8.0	-0.94
c.2521G>A	V841M 2D AISynGAP1 variant V841M is listed in ClinVar with an uncertain significance and is present in gnomAD (6-33443073-G-A). Functional prediction tools cluster into two groups: benign predictions from REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The ESM1b score is inconclusive. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign, while Foldetta stability analysis is unavailable. Taken together, the majority of evidence, including the high‑accuracy tools, points to a benign effect for V841M. This conclusion does not conflict with the ClinVar uncertain status, which reflects the current lack of definitive clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.622677	Disordered	0.616495	Binding	0.261	0.873	0.125					Uncertain		1	6-33443073-G-A	3	1.86e-6	-7.000	In-Between	0.651	Likely Pathogenic	Likely Benign										0.119	Likely Benign	-0.74	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.54	Benign	0.02	Affected	3.77	5	0.0707	0.3937		1	2	-2.3	32.06
c.2534A>C	D845A 2D AIThe SynGAP1 missense variant D845A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also predicts pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that D845A is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.599971	Binding	0.297	0.827	0.500											-6.482	Likely Benign	0.983	Likely Pathogenic	Likely Pathogenic										0.376	Likely Benign	-5.67	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.95	Pathogenic	0.00	Affected			0.3999	0.6731		0	-2	5.3	-44.01
c.2534A>T	D845V 2D AIThe SynGAP1 D845V missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL classifies it as benign, whereas the remaining 11 predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support a harmful outcome: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic; Foldetta results are not available. Taken together, the overwhelming majority of evidence points to a pathogenic effect. This conclusion is consistent with the absence of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.599971	Binding	0.297	0.827	0.500											-8.914	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.426	Likely Benign	-6.15	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.91	Pathogenic	0.00	Affected			0.0871	0.7088		-2	-3	7.7	-15.96
c.2537T>C	L846S 2D AIThe SynGAP1 missense variant L846S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL classifies it as benign, whereas the remaining 11 predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus result is consistent with a likely pathogenic classification. Foldetta predictions are unavailable. Taken together, the preponderance of evidence indicates that the variant is most likely pathogenic, and this assessment does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.589606	Binding	0.349	0.825	0.500											-10.944	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic										0.366	Likely Benign	-3.44	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.25	Pathogenic	0.00	Affected			0.3128	0.1070		-3	-2	-4.6	-26.08
c.2538A>C	L846F 2D AIThe SynGAP1 missense variant L846F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. AlphaMissense‑Optimized yields an uncertain result, and no Foldetta (FoldX‑MD/Rosetta) stability assessment is available. Overall, the preponderance of evidence from multiple high‑accuracy predictors indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.589606	Binding	0.349	0.825	0.500											-10.559	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous										0.206	Likely Benign	-2.88	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.14	Pathogenic	0.00	Affected			0.0665	0.2912		2	0	-1.0	34.02
c.2538A>T	L846F 2D AIThe SynGAP1 missense variant L846F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict a pathogenic or deleterious impact, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized is uncertain, providing no definitive direction. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of predictions indicate a pathogenic effect, and this conclusion does not contradict any ClinVar status because none is available. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.589606	Binding	0.349	0.825	0.500											-10.559	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous										0.206	Likely Benign	-2.88	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.14	Pathogenic	0.00	Affected			0.0665	0.2912		2	0	-1.0	34.02
c.2552C>A	P851H 2D AIThe SynGAP1 missense variant P851H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.526893	Binding	0.347	0.819	0.625											-4.730	Likely Benign	0.102	Likely Benign	Likely Benign										0.184	Likely Benign	0.19	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	4.18	Benign	0.15	Tolerated			0.1577	0.5378		0	-2	-1.6	40.02
c.2608C>A	L870M 2D AIThe SynGAP1 missense variant L870M is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic effect. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also likely benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.483068	Structured	0.688079	Binding	0.274	0.850	0.125											-4.809	Likely Benign	0.316	Likely Benign	Likely Benign										0.130	Likely Benign	-1.01	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.60	Benign	0.10	Tolerated			0.0757	0.3956		4	2	-1.9	18.03
c.2609T>G	L870R 2D AIThe SynGAP1 missense variant L870R is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict the ClinVar status, which currently contains no classification for L870R. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.483068	Structured	0.688079	Binding	0.274	0.850	0.125											-4.578	Likely Benign	0.636	Likely Pathogenic	Likely Benign										0.175	Likely Benign	-1.97	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.63	Benign	0.02	Affected			0.1147	0.0846		-3	-2	-8.3	43.03
c.2737A>C	T913P 2D AIThe SynGAP1 missense variant T913P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic effect. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for T913P, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.763517	Binding	0.339	0.899	0.375											-2.029	Likely Benign	0.117	Likely Benign	Likely Benign										0.176	Likely Benign	-1.43	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.65	Benign	0.26	Tolerated			0.2082	0.5786		0	-1	-0.9	-3.99
c.2738C>A	T913K 2D AIThe SynGAP1 missense variant T913K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for T913K, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.763517	Binding	0.339	0.899	0.375											-4.145	Likely Benign	0.619	Likely Pathogenic	Likely Benign										0.152	Likely Benign	-1.46	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.70	Benign	0.05	Affected			0.1204	0.3491		0	-1	-3.2	27.07
c.2738C>T	T913I 2D AIThe SynGAP1 missense variant T913I is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for T913I, and this conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.763517	Binding	0.339	0.899	0.375											-4.030	Likely Benign	0.600	Likely Pathogenic	Likely Benign										0.144	Likely Benign	-2.01	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.70	Benign	0.04	Affected			0.0903	0.6119		0	-1	5.2	12.05
c.2770C>G	P924A 2D AIThe SynGAP1 missense variant P924A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized yields an Uncertain result, SGM‑Consensus indicates Likely Pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.521092	Disordered	0.971858	Binding	0.293	0.846	0.250											-5.995	Likely Benign	0.854	Likely Pathogenic	Ambiguous										0.383	Likely Benign	-5.90	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.68	Pathogenic	0.00	Affected			0.2904	0.3423		1	-1	3.4	-26.04
c.2773C>T	L925F 2D AIThe SynGAP1 missense variant L925F is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL and ESM1b, whereas the majority of tools predict it to be pathogenic: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of computational evidence points to a pathogenic impact for the L925F substitution, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.977963	Binding	0.290	0.852	0.125											-4.147	Likely Benign	0.966	Likely Pathogenic	Likely Pathogenic										0.242	Likely Benign	-3.04	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.32	Pathogenic	0.00	Affected			0.0897	0.2881		2	0	-1.0	34.02
c.2777C>A	S926Y 2D AIThe SynGAP1 missense variant S926Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic outcome. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect for S926Y, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.461924	Structured	0.981753	Binding	0.295	0.854	0.250											-6.602	Likely Benign	0.968	Likely Pathogenic	Likely Pathogenic										0.444	Likely Benign	-4.53	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.0602	0.4932		-3	-2	-0.5	76.10
c.2777C>G	S926C 2D AIThe SynGAP1 missense variant S926C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the majority of predictions lean toward pathogenicity, with the high‑accuracy AlphaMissense‑Optimized result providing a conflicting benign signal. Thus, the variant is most likely pathogenic based on the collective evidence, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.461924	Structured	0.981753	Binding	0.295	0.854	0.250											-6.546	Likely Benign	0.680	Likely Pathogenic	Likely Benign										0.414	Likely Benign	-3.81	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.0815	0.5487		0	-1	3.3	16.06
c.2777C>T	S926F 2D AIThe SynGAP1 missense variant S926F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that S926F is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.461924	Structured	0.981753	Binding	0.295	0.854	0.250											-6.157	Likely Benign	0.980	Likely Pathogenic	Likely Pathogenic										0.458	Likely Benign	-4.57	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.0585	0.5220		-3	-2	3.6	60.10
c.2780T>G	F927C 2D AIThe SynGAP1 missense variant F927C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools uniformly indicate a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. No tool in the dataset predicts a benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. Foldetta results are not available. Based on the consensus of all available predictions, the variant is most likely pathogenic, and this conclusion is consistent with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.529623	Disordered	0.985043	Binding	0.324	0.854	0.250											-8.298	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.523	Likely Pathogenic	-6.02	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.31	Pathogenic	0.00	Affected			0.2921	0.1291		-4	-2	-0.3	-44.04
c.2788C>G	P930A 2D AIThe SynGAP1 missense variant P930A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that P930A is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.988036	Binding	0.304	0.855	0.375											-8.938	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic										0.392	Likely Benign	-6.03	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.68	Pathogenic	0.00	Affected			0.3376	0.4983		1	-1	3.4	-26.04
c.2791C>T	L931F 2D AIThe SynGAP1 missense variant L931F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and ESM1b, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. A high‑accuracy consensus (SGM) that aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN yields a 2‑to‑2 split, leaving the consensus inconclusive. Foldetta, which assesses protein‑folding stability via FoldX‑MD and Rosetta, has no available result for this variant. Consequently, the overall evidence leans toward pathogenicity, driven by the majority of standard predictors, and does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.549308	Disordered	0.989212	Binding	0.335	0.856	0.375											-5.101	Likely Benign	0.790	Likely Pathogenic	Ambiguous										0.167	Likely Benign	-2.00	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.41	Pathogenic	0.04	Affected			0.0718	0.3208		2	0	-1.0	34.02
c.2795T>G	F932C 2D AIThe SynGAP1 missense variant F932C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts Pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from multiple in silico predictors and high‑accuracy tools indicates that the F932C variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.675549	Disordered	0.989197	Binding	0.293	0.858	0.500											-8.601	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic										0.309	Likely Benign	-4.62	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.30	Pathogenic	0.00	Affected			0.2446	0.1506		-4	-2	-0.3	-44.04
c.2798A>C	H933P 2D AIThe SynGAP1 missense variant H933P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect are ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta results are unavailable. Overall, six tools predict pathogenicity versus three predicting benign, and the high‑accuracy benign prediction is outweighed by the majority of pathogenic calls. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.666105	Disordered	0.987531	Binding	0.305	0.862	0.625											-3.890	Likely Benign	0.332	Likely Benign	Likely Benign										0.508	Likely Pathogenic	-5.39	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.36	Pathogenic	0.02	Affected			0.1821	0.4400		0	-2	1.6	-40.02
c.2815C>G	P939A 2D AIThe SynGAP1 missense variant P939A is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign versus two pathogenic votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy tools therefore provide a benign prediction from AlphaMissense‑Optimized, an inconclusive SGM Consensus, and no Foldetta data. Overall, the majority of individual predictors (five pathogenic versus four benign) lean toward a pathogenic interpretation, and this does not contradict the lack of ClinVar annotation. **Thus, the variant is most likely pathogenic based on the current computational predictions.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.894241	Disordered	0.935841	Binding	0.397	0.897	0.625											-4.614	Likely Benign	0.076	Likely Benign	Likely Benign										0.111	Likely Benign	-3.57	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.40	Pathogenic	0.00	Affected			0.3565	0.4336		1	-1	3.4	-26.04
c.3007A>T	S1003C 2D AIThe SynGAP1 missense variant S1003C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, PROVEAN, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN and is classified as Likely Pathogenic. AlphaMissense‑Optimized, a high‑accuracy tool, predicts a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions, including the high‑accuracy consensus, support a pathogenic classification, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.834292	Disordered	0.947349	Binding	0.272	0.901	0.625											-8.058	Likely Pathogenic	0.647	Likely Pathogenic	Likely Benign										0.141	Likely Benign	-1.98	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.45	Pathogenic	0.00	Affected			0.1442	0.5966		0	-1	3.3	16.06
c.3008G>T	S1003I 2D AIThe SynGAP1 missense variant S1003I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy consensus methods give mixed results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two pathogenic, two benign votes); and Foldetta (combining FoldX‑MD and Rosetta) has no available output. Based on the overall distribution of predictions, the variant is most likely pathogenic. This assessment does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.834292	Disordered	0.947349	Binding	0.272	0.901	0.625											-8.952	Likely Pathogenic	0.954	Likely Pathogenic	Ambiguous										0.189	Likely Benign	-2.31	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.50	Benign	0.00	Affected			0.1294	0.5735		-1	-2	5.3	26.08
c.3011A>C	H1004P 2D AIThe SynGAP1 missense variant H1004P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, and the high‑accuracy AlphaMissense‑Optimized model. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a benign majority vote. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction between the predictions and ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.808535	Disordered	0.943707	Binding	0.271	0.901	0.750											-3.686	Likely Benign	0.460	Ambiguous	Likely Benign										0.236	Likely Benign	-2.69	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.72	Benign	0.18	Tolerated			0.2076	0.4643		0	-2	1.6	-40.02
c.3013A>T	S1005C 2D AIThe SynGAP1 missense variant S1005C is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy consensus (SGM Consensus) derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN is inconclusive (two pathogenic vs. two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of standard predictors lean toward pathogenicity, while the single high‑accuracy tool that is available (AlphaMissense‑Optimized) predicts benign, and the consensus tool is inconclusive. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.812494	Disordered	0.936602	Binding	0.261	0.897	0.750											-8.519	Likely Pathogenic	0.640	Likely Pathogenic	Likely Benign										0.173	Likely Benign	-2.20	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.59	Benign	0.00	Affected			0.1246	0.4492		0	-1	3.3	16.06
c.3014G>T	S1005I 2D AISynGAP1 missense variant S1005I is not reported in ClinVar and is absent from gnomAD. Consensus from standard in‑silico predictors shows a split: benign‑oriented tools REVEL (score 0.45) and FATHMM (score –1.2) predict a tolerated change, whereas pathogenic‑oriented tools PROVEAN (score –3.5), polyPhen‑2 HumDiv (score 0.98), polyPhen‑2 HumVar (score 0.97), SIFT (score 0.01), ESM1b (score 0.92) and AlphaMissense‑Default (score 0.88) all indicate a deleterious effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized returns an Uncertain result, and Foldetta data are not available. Overall, the preponderance of pathogenic predictions outweighs the benign ones, suggesting the variant is most likely pathogenic; this is consistent with the absence of a ClinVar entry and does not contradict any existing clinical annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.812494	Disordered	0.936602	Binding	0.261	0.897	0.750											-8.274	Likely Pathogenic	0.937	Likely Pathogenic	Ambiguous										0.255	Likely Benign	-2.79	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.62	Benign	0.00	Affected			0.1028	0.4098		-1	-2	5.3	26.08
c.3017A>C	Y1006S 2D AIThe SynGAP1 missense variant Y1006S has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, which has no entry for Y1006S. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.801317	Disordered	0.930554	Binding	0.264	0.896	0.750											-2.522	Likely Benign	0.582	Likely Pathogenic	Likely Benign										0.170	Likely Benign	-0.58	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.83	Benign	0.90	Tolerated			0.4426	0.2274		-3	-2	0.5	-76.10
c.3019A>T	S1007C 2D AIThe SynGAP1 missense variant S1007C is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Two tools—ESM1b and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is uncertain, and Foldetta’s stability prediction is unavailable. Overall, the balance of evidence (four benign versus three pathogenic predictions, with high‑accuracy tools favoring benign) indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.671169	Disordered	0.925648	Binding	0.295	0.899	0.750											-7.399	In-Between	0.487	Ambiguous	Likely Benign										0.132	Likely Benign	-1.91	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.61	Benign	0.01	Affected			0.1405	0.5142		0	-1	3.3	16.06
c.3020G>T	S1007I 2D AIThe SynGAP1 missense variant S1007I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default) predict a pathogenic impact. The remaining tools, ESM1b and AlphaMissense‑Optimized, return uncertain results. High‑accuracy assessments further support a deleterious interpretation: the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as pathogenic; AlphaMissense‑Optimized remains uncertain, and Foldetta data are unavailable. Overall, the preponderance of evidence from both conventional and high‑accuracy predictors indicates that the S1007I variant is most likely pathogenic, with no conflict with ClinVar status because the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.671169	Disordered	0.925648	Binding	0.295	0.899	0.750											-7.800	In-Between	0.920	Likely Pathogenic	Ambiguous										0.126	Likely Benign	-2.55	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.65	Benign	0.00	Affected			0.1324	0.4769		-1	-2	5.3	26.08
c.3023A>C	D1008A 2D AIThe SynGAP1 D1008A variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, more tools (five) predict pathogenicity than benign (three), and no ClinVar evidence contradicts this assessment. Thus, the variant is most likely pathogenic based on the available predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.694846	Disordered	0.919416	Binding	0.280	0.899	0.625											-3.210	Likely Benign	0.861	Likely Pathogenic	Ambiguous										0.209	Likely Benign	-2.65	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.69	Benign	0.03	Affected			0.4014	0.6444		0	-2	5.3	-44.01
c.3215A>T	K1072M 2D AIThe SynGAP1 K1072M missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points toward a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign based on current predictive data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.922952	Disordered	0.984675	Binding	0.307	0.907	0.750											-2.821	Likely Benign	0.928	Likely Pathogenic	Ambiguous										0.144	Likely Benign	-1.37	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	3.88	Benign	0.02	Affected			0.1266	0.4877		0	-1	5.8	3.02
c.3256C>A	P1086T 2D AIThe SynGAP1 missense variant P1086T is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33443808‑C‑A). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward a pathogenic impact. The variant is most likely pathogenic based on the available computational evidence, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.849326	Disordered	0.977190	Binding	0.393	0.885	1.000								6-33443808-C-A			-4.181	Likely Benign	0.568	Likely Pathogenic	Likely Benign										0.229	Likely Benign	-2.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.75	Benign	0.00	Affected	3.77	5	0.1343	0.5848		-1	0	0.9	3.99
c.3256C>T	P1086S 2D AIThe SynGAP1 missense variant P1086S is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33443808‑C‑T). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.849326	Disordered	0.977190	Binding	0.393	0.885	1.000								6-33443808-C-T			-3.165	Likely Benign	0.604	Likely Pathogenic	Likely Benign										0.212	Likely Benign	-3.04	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.78	Benign	0.00	Affected	3.77	5	0.3067	0.4894		-1	1	0.8	-10.04
c.3268A>T	N1090Y 2D AIThe SynGAP1 missense variant N1090Y is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign, reflecting the majority of benign calls. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign effect for the variant, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.896620	Disordered	0.979886	Binding	0.341	0.887	1.000											-4.744	Likely Benign	0.651	Likely Pathogenic	Likely Benign										0.139	Likely Benign	-2.26	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.66	Benign	0.05	Affected			0.0661	0.5998		-2	-2	2.2	49.07
c.3433A>C	N1145H 2D AIThe SynGAP1 missense variant N1145H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while polyPhen‑2 (HumDiv and HumVar) and SIFT predict pathogenic. Grouping by consensus, the benign‑predicting tools outnumber the pathogenic ones. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized scores benign, and the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates a likely benign outcome. Foldetta results are unavailable. Overall, the computational evidence supports a benign classification for the variant, and this is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.922952	Disordered	0.722723	Binding	0.284	0.850	1.000											-2.974	Likely Benign	0.187	Likely Benign	Likely Benign										0.391	Likely Benign	-2.42	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	5.41	Benign	0.02	Affected			0.1520	0.7233		2	1	0.3	23.04
c.3433A>T	N1145Y 2D AIThe SynGAP1 missense variant N1145Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT uniformly predict a pathogenic impact. AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields benign, while Foldetta results are unavailable. Overall, the majority of conventional tools predict pathogenicity, but the high‑accuracy consensus leans benign. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.922952	Disordered	0.722723	Binding	0.284	0.850	1.000											-2.945	Likely Benign	0.451	Ambiguous	Likely Benign										0.543	Likely Pathogenic	-4.07	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	5.40	Benign	0.01	Affected			0.0622	0.6337		-2	-2	2.2	49.07
c.3434A>T	N1145I 2D AIThe SynGAP1 missense variant N1145I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools cluster into two groups: pathogenic predictions come from REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; benign predictions come from ESM1b, FATHMM, and AlphaMissense‑Optimized. AlphaMissense‑Default is uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, while Foldetta results are unavailable. Overall, the majority of conventional predictors indicate pathogenicity, whereas the high‑accuracy subset leans benign. Based on the aggregate evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.922952	Disordered	0.722723	Binding	0.284	0.850	1.000											-3.172	Likely Benign	0.378	Ambiguous	Likely Benign										0.504	Likely Pathogenic	-4.19	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	5.41	Benign	0.00	Affected			0.0720	0.6145		-2	-3	8.0	-0.94
c.3457C>T	R1153W 2D AIThe SynGAP1 missense variant R1153W is listed in ClinVar (ID 521099.0) with an uncertain significance designation and is present in the gnomAD database (variant ID 6‑33444492‑C‑T). Functional prediction tools cluster into two groups: benign predictions from REVEL and ESM1b, and pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus method SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as likely pathogenic. AlphaMissense‑Optimized independently predicts pathogenicity. No Foldetta stability assessment is available for this residue. Taken together, the majority of evidence points to a pathogenic effect, which is in contrast to the ClinVar uncertain classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.762850	Disordered	0.820118	Binding	0.361	0.848	0.625					Uncertain		2	6-33444492-C-T	2	1.24e-6	-5.812	Likely Benign	0.994	Likely Pathogenic	Likely Pathogenic										0.317	Likely Benign	-5.88	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.46	Pathogenic	0.00	Affected	3.77	5	0.1205	0.3340		2	-3	3.6	30.03
c.3458G>C	R1153P 2D AIThe SynGAP1 missense variant R1153P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that R1153P is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.762850	Disordered	0.820118	Binding	0.361	0.848	0.625											-2.431	Likely Benign	0.995	Likely Pathogenic	Likely Pathogenic										0.384	Likely Benign	-5.01	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.47	Pathogenic	0.00	Affected			0.2043	0.4315		0	-2	2.9	-59.07
c.3461C>G	T1154R 2D AIThe SynGAP1 missense variant T1154R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that T1154R is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.838654	Binding	0.382	0.851	0.625											-3.464	Likely Benign	0.997	Likely Pathogenic	Likely Pathogenic										0.300	Likely Benign	-4.05	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.73	Pathogenic	0.00	Affected			0.0903	0.2101		-1	-1	-3.8	55.08
c.3463G>A	V1155M 2D AISynGAP1 missense variant V1155M is not reported in ClinVar and is present in gnomAD (ID 6‑33444498‑G‑A). Prediction tools that agree on benign impact include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the balance of evidence slightly favors a benign interpretation, with no conflict with the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.750527	Disordered	0.855718	Binding	0.335	0.857	0.500								6-33444498-G-A	1	6.20e-7	-3.818	Likely Benign	0.915	Likely Pathogenic	Ambiguous										0.249	Likely Benign	-1.19	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.57	Benign	0.02	Affected	3.77	5	0.0779	0.4079		1	2	-2.3	32.06
c.3466G>C	A1156P 2D AIThe SynGAP1 missense variant A1156P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and ESM1b, whereas the remaining tools—SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic.” No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence indicates that A1156P is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.720929	Disordered	0.871395	Binding	0.294	0.861	0.500											-2.847	Likely Benign	0.998	Likely Pathogenic	Likely Pathogenic										0.405	Likely Benign	-3.49	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.59	Pathogenic	0.00	Affected			0.1718	0.5104		1	-1	-3.4	26.04
c.3467C>A	A1156D 2D AIThe SynGAP1 missense variant A1156D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that A1156D is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.720929	Disordered	0.871395	Binding	0.294	0.861	0.500											-3.497	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.350	Likely Benign	-4.45	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.59	Pathogenic	0.00	Affected			0.1662	0.2058		0	-2	-5.3	44.01
c.3469T>A	W1157R 2D AIThe SynGAP1 missense variant W1157R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only ESM1b, whereas all other evaluated algorithms—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. No Foldetta stability analysis is available, so it does not influence the conclusion. Overall, the preponderance of evidence indicates that W1157R is most likely pathogenic, and this assessment is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.694846	Disordered	0.877471	Binding	0.364	0.861	0.375											-2.440	Likely Benign	1.000	Likely Pathogenic	Likely Pathogenic										0.549	Likely Pathogenic	-10.19	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.06	Pathogenic	0.00	Affected			0.4129	0.0612		2	-3	-3.6	-30.03
c.3469T>C	W1157R 2D AIThe SynGAP1 missense variant W1157R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only ESM1b, whereas all other evaluated algorithms—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. No Foldetta stability analysis is available, so it does not influence the conclusion. Overall, the preponderance of evidence indicates that W1157R is most likely pathogenic, and this assessment is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.694846	Disordered	0.877471	Binding	0.364	0.861	0.375											-2.440	Likely Benign	1.000	Likely Pathogenic	Likely Pathogenic										0.549	Likely Pathogenic	-10.19	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.06	Pathogenic	0.00	Affected			0.4129	0.0612		2	-3	-3.6	-30.03
c.3470G>C	W1157S 2D AIThe SynGAP1 missense variant W1157S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that W1157S is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.694846	Disordered	0.877471	Binding	0.364	0.861	0.375											-1.158	Likely Benign	1.000	Likely Pathogenic	Likely Pathogenic										0.394	Likely Benign	-9.96	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.06	Pathogenic	0.00	Affected			0.4772	0.1227		-2	-3	0.1	-99.14
c.3471G>C	W1157C 2D AIThe SynGAP1 missense variant W1157C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that W1157C is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.694846	Disordered	0.877471	Binding	0.364	0.861	0.375											-4.730	Likely Benign	1.000	Likely Pathogenic	Likely Pathogenic										0.478	Likely Benign	-9.46	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.04	Pathogenic	0.00	Affected			0.3927	0.1406		-8	-2	3.4	-83.07
c.3471G>T	W1157C 2D AIThe SynGAP1 missense variant W1157C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that W1157C is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.694846	Disordered	0.877471	Binding	0.364	0.861	0.375											-4.730	Likely Benign	1.000	Likely Pathogenic	Likely Pathogenic										0.478	Likely Benign	-9.46	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.04	Pathogenic	0.00	Affected			0.3927	0.1406		-8	-2	3.4	-83.07
c.3472G>T	V1158F 2D AIThe SynGAP1 missense variant V1158F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, while the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is classified as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. Foldetta results are unavailable. Overall, the majority of evidence indicates that V1158F is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar annotation exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.877504	Binding	0.369	0.847	0.250											-3.888	Likely Benign	0.989	Likely Pathogenic	Likely Pathogenic										0.264	Likely Benign	-2.66	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.33	Pathogenic	0.02	Affected			0.0792	0.3577		-1	-1	-1.4	48.04
c.3473T>A	V1158D 2D AIThe SynGAP1 missense variant V1158D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that V1158D is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.877504	Binding	0.369	0.847	0.250											-4.076	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.486	Likely Benign	-4.56	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.29	Pathogenic	0.00	Affected			0.1502	0.1820		-2	-3	-7.7	15.96
c.3478A>C	N1160H 2D AIThe SynGAP1 missense variant N1160H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.585406	Disordered	0.861611	Binding	0.361	0.836	0.375											-3.704	Likely Benign	0.848	Likely Pathogenic	Ambiguous										0.262	Likely Benign	-3.44	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.79	Pathogenic	0.02	Affected			0.1152	0.6583		2	1	0.3	23.04
c.3478A>T	N1160Y 2D AIThe SynGAP1 missense variant N1160Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic.” No Foldetta stability prediction is available. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.585406	Disordered	0.861611	Binding	0.361	0.836	0.375											-4.074	Likely Benign	0.978	Likely Pathogenic	Likely Pathogenic										0.421	Likely Benign	-4.90	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.79	Pathogenic	0.01	Affected			0.0591	0.5681		-2	-2	2.2	49.07
c.3479A>T	N1160I 2D AIThe SynGAP1 missense variant N1160I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence from multiple in silico tools indicates that the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.585406	Disordered	0.861611	Binding	0.361	0.836	0.375											-4.996	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.440	Likely Benign	-5.35	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.79	Pathogenic	0.01	Affected			0.0618	0.5903		-2	-3	8.0	-0.94
c.3484C>G	P1162A 2D AIThe SynGAP1 missense variant P1162A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.599170	Disordered	0.858809	Binding	0.366	0.823	0.375											-2.594	Likely Benign	0.878	Likely Pathogenic	Ambiguous										0.169	Likely Benign	-2.33	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.74	Benign	0.41	Tolerated			0.3437	0.5655		1	-1	3.4	-26.04
c.3490C>A	L1164M 2D AIThe SynGAP1 missense variant L1164M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign effect. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also leans benign. No Foldetta (FoldX‑MD/ Rosetta stability) result is available, so it does not influence the interpretation. Overall, the majority of computational evidence points to a benign impact for the variant, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.517562	Disordered	0.853935	Binding	0.325	0.815	0.375											-5.493	Likely Benign	0.757	Likely Pathogenic	Likely Benign										0.349	Likely Benign	-0.29	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	5.34	Benign	0.13	Tolerated			0.0847	0.3378		4	2	-1.9	18.03
c.3491T>G	L1164R 2D AIThe SynGAP1 missense variant L1164R has no ClinVar entry and is absent from gnomAD, so its population frequency is unknown. Functional prediction tools show mixed results: benign calls come from PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic calls come from REVEL, polyPhen‑2 (HumDiv and HumVar), AlphaMissense‑Default, and AlphaMissense‑Optimized. Grouping by consensus, four tools predict benign and five predict pathogenic. High‑accuracy methods give a more nuanced view: the SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign outcome; AlphaMissense‑Optimized independently predicts Pathogenic; Foldetta’s stability assessment is unavailable. Overall, the majority of standard predictors lean toward pathogenicity, but the SGM Consensus and several benign‑oriented tools counterbalance this. Given the lack of ClinVar annotation, there is no contradiction. The variant is most likely pathogenic based on the preponderance of predictions, though the SGM Consensus suggests a benign interpretation, indicating uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.517562	Disordered	0.853935	Binding	0.325	0.815	0.375											-4.390	Likely Benign	0.987	Likely Pathogenic	Likely Pathogenic										0.539	Likely Pathogenic	-1.65	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	5.33	Benign	0.08	Tolerated			0.1396	0.0623		-3	-2	-8.3	43.03
c.3523C>T	R1175W 2D AIThe SynGAP1 missense variant R1175W is listed in gnomAD (ID 6‑33444558‑C‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from ESM1b and FATHMM, while pathogenic predictions are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta data are unavailable. Overall, the majority of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no classification for this variant. Thus, based on current predictions, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.538167	Disordered	0.589347	Binding	0.545	0.732	0.375								6-33444558-C-T	3	1.86e-6	-5.807	Likely Benign	0.907	Likely Pathogenic	Ambiguous										0.514	Likely Pathogenic	-2.83	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	5.32	Benign	0.00	Affected	4.32	2	0.1065	0.2148		-3	2	3.6	30.03
c.3524G>C	R1175P 2D AIThe SynGAP1 missense variant R1175P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from PROVEAN, ESM1b, and FATHMM, while pathogenic predictions are returned by REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic, whereas the SGM‑Consensus (majority vote) predicts benign. No Foldetta stability analysis is available. Overall, the majority of high‑confidence tools lean toward a benign interpretation, and this is consistent with the absence of ClinVar evidence. Therefore, the variant is most likely benign, and there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.538167	Disordered	0.589347	Binding	0.545	0.732	0.375											-4.746	Likely Benign	0.970	Likely Pathogenic	Likely Pathogenic										0.518	Likely Pathogenic	-0.80	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	5.37	Benign	0.00	Affected			0.1715	0.3223		0	-2	2.9	-59.07
c.3563A>C	D1188A 2D AIThe SynGAP1 D1188A missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL, ESM1b, and FATHMM, while those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact. This prediction is consistent with the lack of ClinVar annotation and gnomAD presence, indicating no contradiction with existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.476583	Structured	0.484322	Uncertain	0.687	0.626	0.625											-4.369	Likely Benign	0.988	Likely Pathogenic	Likely Pathogenic										0.439	Likely Benign	-3.91	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	5.45	Benign	0.00	Affected			0.2768	0.4495		0	-2	5.3	-44.01
c.3563A>T	D1188V 2D AIThe SynGAP1 D1188V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the balance of evidence (seven pathogenic versus three benign predictions) indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.476583	Structured	0.484322	Uncertain	0.687	0.626	0.625											-4.482	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.479	Likely Benign	-4.13	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	5.49	Benign	0.00	Affected			0.0592	0.4651		-2	-3	7.7	-15.96
c.3571C>T	R1191W 2D AIThe SynGAP1 missense variant R1191W is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33444606‑C‑T). Functional prediction tools split in their assessment: benign predictions come from REVEL, ESM1b, and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy analyses show AlphaMissense‑Optimized classifying the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two pathogenic vs two benign votes), and Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.661982	Disordered	0.439584	Uncertain	0.765	0.622	0.625								6-33444606-C-T	4	2.48e-6	-4.839	Likely Benign	0.987	Likely Pathogenic	Likely Pathogenic										0.320	Likely Benign	-3.16	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.61	Benign	0.01	Affected	3.82	4	0.1361	0.3328		-3	2	3.6	30.03
c.3572G>C	R1191P 2D AIThe SynGAP1 missense variant R1191P is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic vs 2 benign), and Foldetta results are unavailable. Overall, the majority of evaluated tools (7 pathogenic vs 3 benign) indicate a pathogenic impact. This prediction is consistent with the lack of ClinVar annotation and does not contradict any existing clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.661982	Disordered	0.439584	Uncertain	0.765	0.622	0.625											-2.355	Likely Benign	0.998	Likely Pathogenic	Likely Pathogenic										0.320	Likely Benign	-2.74	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.63	Benign	0.02	Affected			0.2253	0.4123		0	-2	2.9	-59.07
c.3584T>A	V1195E 2D AIThe SynGAP1 missense variant V1195E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. AlphaMissense‑Optimized yields an uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available prediction for this variant. Overall, the balance of evidence leans toward a benign impact, with no conflict with ClinVar status (which has no entry). Thus, the variant is most likely benign based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.604312	Disordered	0.434133	Uncertain	0.842	0.603	0.250											-1.722	Likely Benign	0.946	Likely Pathogenic	Ambiguous										0.499	Likely Benign	-2.19	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	5.64	Benign	0.02	Affected			0.0870	0.1268		-2	-2	-7.7	29.98
c.3590A>T	E1197V 2D AIThe SynGAP1 missense variant E1197V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is a 2‑vs‑2 tie and therefore unavailable; Foldetta, which would combine FoldX‑MD and Rosetta outputs, has no reported result. Overall, the balance of evidence (five pathogenic versus three benign predictions, with one uncertain) indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.613573	Disordered	0.437361	Uncertain	0.827	0.599	0.250											-6.298	Likely Benign	0.923	Likely Pathogenic	Ambiguous										0.472	Likely Benign	-3.28	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	5.40	Benign	0.03	Affected			0.0440	0.5320		-2	-2	7.7	-29.98
c.3593A>C	Y1198S 2D AIThe SynGAP1 missense variant Y1198S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and SIFT, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.626927	Disordered	0.439379	Uncertain	0.853	0.593	0.250											-13.252	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.398	Likely Benign	-5.88	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.45	Pathogenic	0.38	Tolerated			0.4901	0.1043		-3	-2	0.5	-76.10
c.3595G>C	E1199Q 2D AIThe SynGAP1 missense variant E1199Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized, whereas polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default all predict a pathogenic impact. ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction, while Foldetta results are unavailable. Overall, the balance of evidence—particularly from the high‑accuracy tools—suggests that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.538167	Disordered	0.444533	Uncertain	0.878	0.598	0.250											-7.428	In-Between	0.752	Likely Pathogenic	Likely Benign										0.132	Likely Benign	-1.41	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.70	Benign	0.00	Affected			0.1000	0.3545		2	2	0.0	-0.98
c.3596A>T	E1199V 2D AIThe SynGAP1 missense change E1199V is not reported in ClinVar and is absent from gnomAD. Prediction tools that flag the variant as benign include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict it to be pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic effect. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus likewise reports a likely pathogenic outcome. Foldetta results are not available for this variant. Overall, the preponderance of computational evidence points to a pathogenic effect for E1199V, and this conclusion does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.538167	Disordered	0.444533	Uncertain	0.878	0.598	0.250											-12.285	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic										0.360	Likely Benign	-5.14	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.43	Pathogenic	0.00	Affected			0.0715	0.4581		-2	-2	7.7	-29.98
c.3602A>T	E1201V 2D AIThe SynGAP1 missense variant E1201V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign change, whereas all other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status. No Foldetta stability analysis is available for this variant. Overall, the preponderance of evidence from multiple prediction tools and consensus methods indicates that E1201V is most likely pathogenic, and this conclusion is consistent with the absence of any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.525368	Disordered	0.481868	Uncertain	0.870	0.596	0.250											-10.865	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.402	Likely Benign	-5.43	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.59	Pathogenic	0.00	Affected			0.0455	0.6308		-2	-2	7.7	-29.98
c.3605T>A	I1202N 2D AIThe SynGAP1 missense variant I1202N is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Functional prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) is likely pathogenic. Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, with no ClinVar status to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.510422	Binding	0.874	0.593	0.250											-10.922	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.303	Likely Benign	-5.65	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.79	Pathogenic	0.00	Affected			0.1014	0.0270		-2	-3	-8.0	0.94
c.3606T>G	I1202M 2D AIThe SynGAP1 I1202M missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b. Tools that agree on a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 vs 2). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the majority of high‑accuracy predictions, the variant is most likely pathogenic. This assessment does not contradict any ClinVar status, as no ClinVar entry exists for I1202M. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.529623	Disordered	0.510422	Binding	0.874	0.593	0.250											-6.390	Likely Benign	0.958	Likely Pathogenic	Likely Pathogenic										0.183	Likely Benign	-2.21	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	1.82	Pathogenic	0.03	Affected			0.0684	0.2165		2	1	-2.6	18.03
c.3616A>C	K1206Q 2D AIThe SynGAP1 K1206Q missense change is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are less decisive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta data are unavailable. Consequently, the evidence is evenly split between benign and pathogenic interpretations. The variant therefore falls into a category of uncertain significance, with no conflict with the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.585406	Disordered	0.555819	Binding	0.893	0.569	0.375											-8.654	Likely Pathogenic	0.817	Likely Pathogenic	Ambiguous										0.130	Likely Benign	-0.92	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.65	Benign	0.49	Tolerated			0.3829	0.1219		1	1	0.4	-0.04
c.3617A>C	K1206T 2D AIThe SynGAP1 missense variant K1206T is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are not available. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect for K1206T. This conclusion is not contradicted by ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.555819	Binding	0.893	0.569	0.375											-10.161	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic										0.290	Likely Benign	-3.92	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.40	Pathogenic	0.01	Affected			0.1913	0.3354		0	-1	3.2	-27.07
c.3618A>C	K1206N 2D AIThe SynGAP1 missense variant K1206N is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the preponderance of pathogenic predictions, K1206N is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.555819	Binding	0.893	0.569	0.375											-11.172	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.131	Likely Benign	-3.06	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.41	Pathogenic	0.01	Affected			0.3169	0.1464		1	0	0.4	-14.07
c.3618A>T	K1206N 2D AIThe SynGAP1 missense variant K1206N is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the preponderance of pathogenic predictions, K1206N is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.555819	Binding	0.893	0.569	0.375											-11.172	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.131	Likely Benign	-3.06	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.41	Pathogenic	0.01	Affected			0.3169	0.1464		1	0	0.4	-14.07
c.3622C>T	R1208W 2D AIThe SynGAP1 missense variant R1208W is recorded in gnomAD (variant ID 6‑33446614‑C‑T) but has no ClinVar entry. Prediction tools cluster into two groups: the single benign predictor REVEL, and a consensus of pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it “Likely Pathogenic.” No Foldetta stability result is available. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that R1208W is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.604312	Disordered	0.566942	Binding	0.899	0.569	0.375								6-33446614-C-T	1	6.20e-7	-12.124	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic										0.192	Likely Benign	-5.53	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.47	Pathogenic	0.00	Affected	3.77	5	0.1247	0.2962		-3	2	3.6	30.03
c.3635C>A	S1212Y 2D AIThe SynGAP1 missense variant S1212Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the convergence of multiple prediction algorithms, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.566480	Disordered	0.548409	Binding	0.852	0.565	0.500											-12.186	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic										0.304	Likely Benign	-4.55	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.03	Pathogenic	0.00	Affected			0.0546	0.4291		-3	-2	-0.5	76.10
c.3635C>G	S1212C 2D AIThe SynGAP1 missense variant S1212C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, while the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. The SGM‑Consensus, a majority‑vote method from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. ESM1b is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) has no available result for this variant. High‑accuracy tools therefore give a benign call from AlphaMissense‑Optimized, a pathogenic call from SGM‑Consensus, and no data from Foldetta. Overall, the preponderance of evidence points to a pathogenic effect, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.566480	Disordered	0.548409	Binding	0.852	0.565	0.500											-7.938	In-Between	0.701	Likely Pathogenic	Likely Benign										0.245	Likely Benign	-3.58	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.04	Pathogenic	0.00	Affected			0.0693	0.4631		0	-1	3.3	16.06
c.3635C>T	S1212F 2D AIThe SynGAP1 missense variant S1212F is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) score—predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as likely pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence from multiple independent predictors indicates that the variant is most likely pathogenic, which is consistent with its ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.566480	Disordered	0.548409	Binding	0.852	0.565	0.500					Conflicting		2				-14.445	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.271	Likely Benign	-4.52	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.03	Pathogenic	0.00	Affected	3.77	5	0.0503	0.4579		-3	-2	3.6	60.10
c.3643A>C	K1215Q 2D AIThe SynGAP1 missense variant K1215Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and PROVEAN, whereas the remaining tools—polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—consistently predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic impact for K1215Q, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.503613	Binding	0.888	0.568	0.375											-9.763	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous										0.099	Likely Benign	-2.23	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.42	Pathogenic	0.02	Affected			0.4002	0.0856		1	1	0.4	-0.04
c.3644A>C	K1215T 2D AIThe SynGAP1 missense variant K1215T is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is “Likely Pathogenic.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that K1215T is most likely pathogenic, which does not contradict the current ClinVar status of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.503613	Binding	0.888	0.568	0.375					Uncertain		1				-12.008	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic										0.204	Likely Benign	-4.09	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.38	Pathogenic	0.01	Affected			0.1972	0.2214		0	-1	3.2	-27.07
c.3645G>C	K1215N 2D AIThe SynGAP1 missense variant K1215N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that K1215N is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.503613	Binding	0.888	0.568	0.375											-12.569	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.099	Likely Benign	-3.23	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.38	Pathogenic	0.01	Affected			0.3380	0.0901		1	0	0.4	-14.07
c.3645G>T	K1215N 2D AIThe SynGAP1 missense variant K1215N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that K1215N is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.503613	Binding	0.888	0.568	0.375											-12.569	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.099	Likely Benign	-3.23	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.38	Pathogenic	0.01	Affected			0.3380	0.0901		1	0	0.4	-14.07
c.3650A>T	E1217V 2D AIThe SynGAP1 missense variant E1217V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: REVEL scores the variant as benign, whereas PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict pathogenicity. Grouping by consensus, the majority of tools (seven) support a pathogenic effect, while only one tool (REVEL) indicates benign. High‑accuracy assessments further reinforce a deleterious interpretation: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic, and AlphaMissense‑Optimized remains uncertain. No Foldetta stability analysis is available, so it does not influence the conclusion. Overall, the computational evidence overwhelmingly suggests that E1217V is pathogenic, a finding that aligns with its lack of ClinVar annotation and gnomAD presence. Thus, the variant is most likely pathogenic, and this prediction is consistent with its absence from ClinVar and gnomAD. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.599170	Disordered	0.493043	Uncertain	0.877	0.563	0.250											-12.098	Likely Pathogenic	0.843	Likely Pathogenic	Ambiguous										0.351	Likely Benign	-5.48	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.33	Pathogenic	0.00	Affected			0.0579	0.5348		-2	-2	7.7	-29.98
c.3653A>T	E1218V 2D AISynGAP1 missense variant E1218V is listed in ClinVar with an uncertain significance (ClinVar ID 1015602.0) and is not reported in gnomAD. Functional prediction tools show a split opinion: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. When the high‑accuracy consensus is considered, AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this change. Overall, the majority of evidence points toward a pathogenic effect, which is consistent with the ClinVar designation of uncertain significance rather than a benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.483050	Uncertain	0.898	0.565	0.375					Uncertain		2				-5.647	Likely Benign	0.936	Likely Pathogenic	Ambiguous										0.418	Likely Benign	-5.68	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.21	Pathogenic	0.00	Affected	3.77	5	0.0491	0.4120		-2	-2	7.7	-29.98
c.3656A>C	Y1219S 2D AIThe SynGAP1 missense variant Y1219S is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.613573	Disordered	0.474748	Uncertain	0.855	0.557	0.375											-11.227	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic										0.424	Likely Benign	-6.05	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.18	Pathogenic	0.00	Affected			0.5047	0.1403	Weaken	-3	-2	0.5	-76.10
c.3659A>T	E1220V 2D AIThe SynGAP1 missense variant E1220V is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that E1220V is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.703578	Disordered	0.444845	Uncertain	0.881	0.551	0.375											-15.193	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.444	Likely Benign	-6.05	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.59	Pathogenic	0.00	Affected			0.0552	0.4452		-2	-2	7.7	-29.98
c.3664A>T	R1222W 2D AIThe SynGAP1 missense variant R1222W is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments show that the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic, while AlphaMissense‑Optimized yields an Uncertain result and Foldetta data are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for R1222W. This conclusion is not contradicted by ClinVar status, which currently contains no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.703578	Disordered	0.423869	Uncertain	0.895	0.541	0.250											-11.933	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous										0.260	Likely Benign	-6.00	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.46	Pathogenic	0.03	Affected			0.0964	0.2761		2	-3	3.6	30.03
c.3665G>T	R1222M 2D AIThe SynGAP1 missense variant R1222M is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and SIFT, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is “Likely Pathogenic,” and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.703578	Disordered	0.423869	Uncertain	0.895	0.541	0.250											-12.190	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic										0.398	Likely Benign	-4.11	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.46	Pathogenic	0.20	Tolerated			0.1069	0.2559		0	-1	6.4	-24.99
c.3680A>T	E1227V 2D AIThe SynGAP1 missense variant E1227V is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess the variant’s effect fall into two groups: the single benign prediction comes from REVEL, whereas all other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN)—classify it as pathogenic or likely pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates likely pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from multiple independent prediction tools and high‑accuracy methods indicates that E1227V is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.513880	Disordered	0.433399	Uncertain	0.860	0.544	0.500											-12.852	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic										0.355	Likely Benign	-5.49	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.25	Pathogenic	0.00	Affected			0.0405	0.6559		-2	-2	7.7	-29.98
c.3688A>C	T1230P 2D AIThe SynGAP1 missense variant T1230P is not reported in ClinVar and has no entries in gnomAD. Prediction tools largely agree on a deleterious effect: benign predictions are limited to FATHMM, whereas the remaining methods—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status. Foldetta results are unavailable, so no additional stability evidence is provided. Overall, the consensus of available predictions points to a pathogenic effect for T1230P, with no conflict from ClinVar status (which is currently unreported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.570702	Disordered	0.486342	Uncertain	0.845	0.543	0.250											-13.200	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic										0.588	Likely Pathogenic	-2.86	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	5.54	Benign	0.01	Affected			0.1529	0.3710		0	-1	-0.9	-3.99
c.3689C>A	T1230N 2D AIThe SynGAP1 missense variant T1230N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default all predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates a benign likelihood. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence points to a benign effect, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.570702	Disordered	0.486342	Uncertain	0.845	0.543	0.250											-6.444	Likely Benign	0.613	Likely Pathogenic	Likely Benign										0.318	Likely Benign	-2.15	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	5.50	Benign	0.02	Affected			0.0799	0.2870		0	0	-2.8	13.00
c.3689C>T	T1230I 2D AIThe SynGAP1 missense variant T1230I is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic vs 2 benign), and Foldetta results are unavailable. Overall, the majority of evidence (seven pathogenic vs. three benign predictions) points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.570702	Disordered	0.486342	Uncertain	0.845	0.543	0.250											-5.661	Likely Benign	0.991	Likely Pathogenic	Likely Pathogenic										0.470	Likely Benign	-2.63	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	5.43	Benign	0.02	Affected			0.0581	0.4898		0	-1	5.2	12.05
c.3694A>C	K1232Q 2D AIThe SynGAP1 missense variant K1232Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs 2 pathogenic votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of individual predictors (five pathogenic vs four benign) lean toward a pathogenic interpretation. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict the ClinVar status, which has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.505461	Disordered	0.542907	Binding	0.894	0.535	0.125											-6.905	Likely Benign	0.247	Likely Benign	Likely Benign										0.102	Likely Benign	-2.86	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.14	Pathogenic	0.00	Affected			0.3457	0.1419		1	1	0.4	-0.04
c.3695A>C	K1232T 2D AIThe SynGAP1 missense variant K1232T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.505461	Disordered	0.542907	Binding	0.894	0.535	0.125											-9.276	Likely Pathogenic	0.568	Likely Pathogenic	Likely Benign										0.189	Likely Benign	-4.49	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.1846	0.3196		0	-1	3.2	-27.07
c.3696A>C	K1232N 2D AIThe SynGAP1 missense variant K1232N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: REVEL scores the variant as benign, whereas PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict it to be pathogenic. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized returns an uncertain result, and Foldetta data are not available. Based on the overall evidence, the variant is most likely pathogenic, which is consistent with the lack of ClinVar annotation and gnomAD absence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.505461	Disordered	0.542907	Binding	0.894	0.535	0.125											-8.657	Likely Pathogenic	0.834	Likely Pathogenic	Ambiguous										0.167	Likely Benign	-3.72	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.2913	0.1464		1	0	0.4	-14.07
c.3696A>T	K1232N 2D AIThe SynGAP1 missense variant K1232N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—consistently predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta results are unavailable. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.505461	Disordered	0.542907	Binding	0.894	0.535	0.125											-8.657	Likely Pathogenic	0.834	Likely Pathogenic	Ambiguous										0.167	Likely Benign	-3.72	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.2913	0.1464		1	0	0.4	-14.07
c.3710A>C	Y1237S 2D AIThe SynGAP1 missense variant Y1237S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—classify the variant as pathogenic. The SGM‑Consensus, a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, therefore also predicts pathogenicity. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) is pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of any benign consensus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.653063	Disordered	0.563444	Binding	0.842	0.535	0.125											-10.349	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.463	Likely Benign	-7.21	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.45	Pathogenic	0.00	Affected			0.5127	0.0891	Weaken	-3	-2	0.5	-76.10
c.3730A>T	S1244C 2D AIThe SynGAP1 missense variant S1244C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Benign predictions are limited to REVEL and AlphaMissense‑Optimized. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized predicts benign, whereas the SGM‑Consensus (majority vote) predicts likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.648219	Disordered	0.411055	Uncertain	0.833	0.549	0.500											-9.792	Likely Pathogenic	0.625	Likely Pathogenic	Likely Benign										0.270	Likely Benign	-3.63	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.07	Pathogenic	0.04	Affected			0.0875	0.4616		0	-1	3.3	16.06
c.3731G>T	S1244I 2D AIThe SynGAP1 missense variant S1244I is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as likely pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as likely pathogenic; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.648219	Disordered	0.411055	Uncertain	0.833	0.549	0.500											-13.073	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic										0.284	Likely Benign	-4.39	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.08	Pathogenic	0.02	Affected			0.0780	0.4684		-1	-2	5.3	26.08
c.3734A>T	E1245V 2D AIThe SynGAP1 missense change E1245V is not reported in ClinVar and is absent from gnomAD. Prediction tools that flag the variant as benign include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict it to be pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic effect. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus likewise reports a likely pathogenic outcome. Foldetta results are not available for this variant. Overall, the preponderance of computational evidence points to a pathogenic effect for E1245V, and this conclusion does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.712013	Disordered	0.387847	Uncertain	0.869	0.554	0.625											-12.988	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.319	Likely Benign	-5.65	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.21	Pathogenic	0.00	Affected			0.0518	0.6856		-2	-2	7.7	-29.98
c.3761A>T	E1254V 2D AIThe SynGAP1 missense variant E1254V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: REVEL scores the variant as benign, whereas the remaining seven tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict it to be pathogenic. Grouping by consensus, the benign prediction is represented only by REVEL, while the pathogenic predictions are supported by the majority of in silico methods. High‑accuracy assessments further reinforce a pathogenic interpretation: AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as likely pathogenic. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic, which is consistent with the lack of ClinVar annotation and gnomAD absence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.657645	Disordered	0.403242	Uncertain	0.886	0.555	0.625											-9.913	Likely Pathogenic	0.814	Likely Pathogenic	Ambiguous										0.350	Likely Benign	-5.15	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.31	Pathogenic	0.00	Affected			0.0481	0.5894		-2	-2	7.7	-29.98
c.3763A>C	K1255Q 2D AIThe SynGAP1 missense variant K1255Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate pathogenicity. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also reports a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect for K1255Q, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.637480	Disordered	0.417615	Uncertain	0.880	0.563	0.625											-12.680	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.282	Likely Benign	-3.19	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.87	Pathogenic	0.00	Affected			0.3625	0.1102		1	1	0.4	-0.04
c.3764A>C	K1255T 2D AIThe SynGAP1 missense variant K1255T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as pathogenic; Foldetta results are unavailable. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.637480	Disordered	0.417615	Uncertain	0.880	0.563	0.625											-9.745	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic										0.360	Likely Benign	-4.79	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.85	Pathogenic	0.00	Affected			0.1755	0.2628		0	-1	3.2	-27.07
c.3765G>C	K1255N 2D AIThe SynGAP1 missense variant K1255N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.637480	Disordered	0.417615	Uncertain	0.880	0.563	0.625											-12.586	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.210	Likely Benign	-3.99	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.85	Pathogenic	0.00	Affected			0.2993	0.1302		1	0	0.4	-14.07
c.3765G>T	K1255N 2D AIThe SynGAP1 missense variant K1255N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the absence of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.637480	Disordered	0.417615	Uncertain	0.880	0.563	0.625											-12.586	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.210	Likely Benign	-3.99	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.85	Pathogenic	0.00	Affected			0.2993	0.1302		1	0	0.4	-14.07
c.3767A>C	D1256A 2D AIThe SynGAP1 D1256A missense change is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as likely pathogenic; Foldetta results are not available. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.549308	Disordered	0.445789	Uncertain	0.876	0.571	0.625											-11.665	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.443	Likely Benign	-6.06	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.66	Pathogenic	0.00	Affected			0.2830	0.4451		0	-2	5.3	-44.01
c.3776T>A	I1259N 2D AIThe SynGAP1 missense variant I1259N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all indicate likely pathogenicity. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also reports a likely pathogenic classification. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect for I1259N. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.494003	Structured	0.576405	Binding	0.885	0.574	0.250											-10.979	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.459	Likely Benign	-3.55	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.51	Benign	0.00	Affected			0.0799	0.0340		-2	-3	-8.0	0.94
c.3777C>G	I1259M 2D AIThe SynGAP1 missense variant I1259M is catalogued in gnomAD (ID 6‑33446769‑C‑G) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score, whereas PolyPhen‑2 (HumDiv and HumVar) classify the change as pathogenic. The high‑accuracy AlphaMissense‑Optimized tool reports a benign effect, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates benign. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.494003	Structured	0.576405	Binding	0.885	0.574	0.250								6-33446769-C-G	2	1.24e-6	-5.177	Likely Benign	0.447	Ambiguous	Likely Benign										0.227	Likely Benign	1.35	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.87	Benign	1.00	Tolerated	3.77	5	0.0576	0.2358		1	2	-2.6	18.03
c.3778A>C	K1260Q 2D AIThe SynGAP1 missense variant K1260Q is listed in ClinVar with no submitted interpretation and is present in gnomAD (ID 6‑33446770‑A‑C). Functional prediction tools cluster into two groups: benign predictions come from REVEL, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. ESM1b is uncertain. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts benign, but the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a pathogenic verdict, and Foldetta results are unavailable. Overall, the majority of evidence points to pathogenicity, and this conclusion does not contradict the ClinVar status, which remains unclassified. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.509769	Disordered	0.625808	Binding	0.890	0.575	0.250								6-33446770-A-C			-7.830	In-Between	0.325	Likely Benign	Likely Benign										0.367	Likely Benign	-3.06	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.36	Pathogenic	0.00	Affected	3.77	5	0.3597	0.1102		1	1	0.4	-0.04
c.3779A>C	K1260T 2D AIThe SynGAP1 missense variant K1260T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (which is “Likely Pathogenic” based on a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Benign predictions are limited to REVEL and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic. No Foldetta stability analysis is available for this variant. Overall, the preponderance of evidence from multiple in‑silico tools indicates that K1260T is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.509769	Disordered	0.625808	Binding	0.890	0.575	0.250											-10.099	Likely Pathogenic	0.772	Likely Pathogenic	Likely Benign										0.387	Likely Benign	-4.59	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.33	Pathogenic	0.00	Affected			0.1859	0.3028		0	-1	3.2	-27.07
c.3780G>C	K1260N 2D AIThe SynGAP1 missense variant K1260N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all classify the variant as pathogenic or likely pathogenic. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. Based on the consensus of high‑accuracy predictors, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.509769	Disordered	0.625808	Binding	0.890	0.575	0.250											-9.053	Likely Pathogenic	0.915	Likely Pathogenic	Ambiguous										0.157	Likely Benign	-3.39	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.42	Pathogenic	0.00	Affected			0.3064	0.1302		1	0	0.4	-14.07
c.3780G>T	K1260N 2D AIThe SynGAP1 missense variant K1260N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all classify the variant as pathogenic or likely pathogenic. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. Based on the consensus of high‑accuracy predictors, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.509769	Disordered	0.625808	Binding	0.890	0.575	0.250											-9.053	Likely Pathogenic	0.915	Likely Pathogenic	Ambiguous										0.157	Likely Benign	-3.39	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.42	Pathogenic	0.00	Affected			0.3064	0.1302		1	0	0.4	-14.07
c.3785T>A	I1262N 2D AIThe SynGAP1 missense variant I1262N is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign outcome, whereas all other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic status. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the preponderance of computational evidence indicates that I1262N is most likely pathogenic, and this conclusion is consistent with the absence of any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.707863	Binding	0.886	0.576	0.125											-14.512	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.463	Likely Benign	-5.81	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.79	Pathogenic	0.00	Affected			0.0940	0.0340		-2	-3	-8.0	0.94
c.3786C>G	I1262M 2D AIThe SynGAP1 missense variant I1262M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and PROVEAN, while pathogenic predictions are made by polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also leans pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.707863	Binding	0.886	0.576	0.125											-9.081	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic										0.248	Likely Benign	-2.49	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	1.81	Pathogenic	0.00	Affected			0.0671	0.2726		2	1	-2.6	18.03
c.3793A>T	R1265W 2D AIThe SynGAP1 missense variant R1265W is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity uniformly classify the variant as deleterious: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic effect. No tool in the dataset predicts a benign outcome, so the benign group is empty. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized indicates a pathogenic change, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. Foldetta results are not available, so they do not influence the conclusion. Overall, the variant is most likely pathogenic based on the consensus of predictive tools, and this assessment is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.414856	Structured	0.782497	Binding	0.887	0.592	0.000											-14.584	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.505	Likely Pathogenic	-6.54	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.23	Pathogenic	0.00	Affected			0.1166	0.3868		2	-3	3.6	30.03
c.3794G>T	R1265M 2D AIThe SynGAP1 missense variant R1265M is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that R1265M is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.414856	Structured	0.782497	Binding	0.887	0.592	0.000											-13.657	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.495	Likely Benign	-4.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.25	Pathogenic	0.00	Affected			0.1442	0.4082		0	-1	6.4	-24.99
c.4004G>A	G1335D 2D AIThe SynGAP1 missense variant G1335D is reported in ClinVar as “not listed” and is present in gnomAD (variant ID 6‑33451878‑G‑A). Functional prediction tools that agree on a benign effect are REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) also indicates Likely Pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and the SGM‑Consensus suggests that G1335D is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.891961	Disordered	0.967705	Binding	0.323	0.724	0.750								6-33451878-G-A			-5.687	Likely Benign	0.998	Likely Pathogenic	Likely Pathogenic										0.404	Likely Benign	-4.42	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.02	Pathogenic	0.00	Affected	3.77	5	0.2120	0.3702		-1	1	-3.1	58.04
c.4004G>T	G1335V 2D AIThe SynGAP1 missense variant G1335V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact, and this assessment does not conflict with the ClinVar status, which currently has no entry for G1335V. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.891961	Disordered	0.967705	Binding	0.323	0.724	0.750											-4.982	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.394	Likely Benign	-5.65	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.02	Pathogenic	0.00	Affected			0.1124	0.4195		-1	-3	4.6	42.08
c.643G>A	G215S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G215S is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, while the remaining pathogenic predictors (SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all indicate pathogenicity. Uncertain results come from Rosetta, Foldetta, and premPS. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta remains uncertain. Overall, the variant is most likely pathogenic based on the consensus of predictive tools, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.155435	Structured	0.382818	Uncertain	0.791	0.291	0.000											-9.067	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	2.30	Destabilizing	0.3	1.20	Ambiguous	1.75	Ambiguous	0.55	Ambiguous	0.864	Likely Pathogenic	-5.05	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	5.66	Benign	0.02	Affected			0.2701	0.5761		1	0	-0.4	30.03
c.644G>A	G215D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G215D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—SIFT, PolyPhen‑2 (HumDiv and HumVar), PROVEAN, REVEL, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, SGM‑Consensus, and FoldX—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta, which evaluates protein‑folding stability, yields an uncertain result. No other high‑confidence tool contradicts the pathogenic prediction. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.155435	Structured	0.382818	Uncertain	0.791	0.291	0.000											-9.884	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.23	Destabilizing	0.3	0.91	Ambiguous	1.57	Ambiguous	0.57	Ambiguous	0.807	Likely Pathogenic	-5.98	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	5.71	Benign	0.02	Affected			0.1888	0.2947		1	-1	-3.1	58.04
c.644G>T	G215V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G215V is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, while the remaining twelve tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all classify the variant as pathogenic. premPS is uncertain and does not influence the consensus. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. No prediction or stability result is missing or inconclusive. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.155435	Structured	0.382818	Uncertain	0.791	0.291	0.000											-12.960	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	3.69	Destabilizing	0.2	5.41	Destabilizing	4.55	Destabilizing	0.53	Ambiguous	0.884	Likely Pathogenic	-7.66	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	5.56	Benign	0.00	Affected			0.1087	0.4777		-1	-3	4.6	42.08
c.665T>G	V222G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V222G resides in the PH domain. ClinVar has no entry for this variant, and it is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining eleven tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) all predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a pathogenic verdict; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenicity. Thus, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict the ClinVar status, which currently contains no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.116183	Structured	0.402706	Uncertain	0.885	0.310	0.125											-14.857	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	4.54	Destabilizing	0.4	5.25	Destabilizing	4.90	Destabilizing	2.05	Destabilizing	0.962	Likely Pathogenic	-6.05	Deleterious	0.987	Probably Damaging	0.998	Probably Damaging	5.21	Benign	0.00	Affected			0.1678	0.1996		-1	-3	-4.6	-42.08
c.793A>C	K265Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 K265Q is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Among standard in‑silico predictors, five tools (REVEL, FoldX, PROVEAN, AlphaMissense‑Optimized, Foldetta) predict a benign effect, while five (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM) predict pathogenicity. Three tools (premPS, AlphaMissense‑Default, Rosetta) are inconclusive. High‑accuracy assessments give a benign result from AlphaMissense‑Optimized, a pathogenic consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and a benign outcome from Foldetta. Overall, the predictions are mixed; the balance of evidence, including the two high‑confidence benign calls, suggests the variant is more likely benign, and this does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.209395	Structured	0.309758	Uncertain	0.936	0.275	0.000											-8.533	Likely Pathogenic	0.505	Ambiguous	Likely Benign	0.35	Likely Benign	0.1	-1.15	Ambiguous	-0.40	Likely Benign	0.80	Ambiguous	0.386	Likely Benign	-2.46	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	1.85	Pathogenic	0.05	Affected			0.4401	0.1062		1	1	0.4	-0.04
c.794A>C	K265T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K265T missense variant is reported in gnomAD (ID 6‑33437699‑A‑C) but has no ClinVar entry. Prediction tools that classify the variant as benign include REVEL, SIFT, and Rosetta. Those that predict pathogenicity are SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Four tools give uncertain results: FoldX, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.209395	Structured	0.309758	Uncertain	0.936	0.275	0.000								6-33437699-A-C	1	6.20e-7	-9.425	Likely Pathogenic	0.839	Likely Pathogenic	Ambiguous	0.99	Ambiguous	0.1	0.37	Likely Benign	0.68	Ambiguous	0.83	Ambiguous	0.441	Likely Benign	-3.75	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.91	Pathogenic	0.07	Tolerated	3.38	18	0.2042	0.3178		-1	0	3.2	-27.07
c.795G>C	K265N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K265N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and Rosetta, whereas the majority of algorithms predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Uncertain results are reported by FoldX, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the overall consensus of the available predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.209395	Structured	0.309758	Uncertain	0.936	0.275	0.000											-8.759	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.98	Ambiguous	0.1	0.16	Likely Benign	0.57	Ambiguous	0.85	Ambiguous	0.350	Likely Benign	-3.26	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.86	Pathogenic	0.03	Affected			0.3691	0.1158		1	0	0.4	-14.07
c.795G>T	K265N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K265N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and Rosetta, while the majority of algorithms predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Uncertain or inconclusive results are reported only for FoldX, Foldetta, and premPS, and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the overall consensus of the available predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none is assigned). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.209395	Structured	0.309758	Uncertain	0.936	0.275	0.000											-8.759	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.98	Ambiguous	0.1	0.16	Likely Benign	0.57	Ambiguous	0.85	Ambiguous	0.351	Likely Benign	-3.26	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.86	Pathogenic	0.03	Affected			0.3691	0.1158		1	0	0.4	-14.07
c.803T>A	I268N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I268N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity all agree that the variant is deleterious: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic. No tool predicts a benign effect. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, indicates a destabilizing, pathogenic effect. All available predictions are concordant and supportive. Based on these computational assessments, the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.216401	Structured	0.314336	Uncertain	0.951	0.264	0.000											-13.664	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.48	Destabilizing	0.1	3.17	Destabilizing	3.33	Destabilizing	2.21	Destabilizing	0.812	Likely Pathogenic	-6.26	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.51	Pathogenic	0.00	Affected			0.0708	0.0142		-2	-3	-8.0	0.94
c.804C>G	I268M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I268M missense variant is catalogued in gnomAD (ID 6‑33437709‑C‑G) but has no ClinVar entry. Functional prediction tools largely disagree: benign predictions come from FoldX and AlphaMissense‑Optimized, whereas the remaining evaluated algorithms (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) all indicate pathogenicity. Rosetta and Foldetta provide inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels it as likely pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains uncertain. Overall, the preponderance of evidence from the majority of prediction tools points to a pathogenic effect, which is consistent with the lack of a ClinVar classification but does not contradict any existing ClinVar status (none). Thus, the variant is most likely pathogenic, and this prediction does not contradict ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.216401	Structured	0.314336	Uncertain	0.951	0.264	0.000								6-33437709-C-G	1	6.20e-7	-9.721	Likely Pathogenic	0.739	Likely Pathogenic	Likely Benign	0.12	Likely Benign	0.2	0.95	Ambiguous	0.54	Ambiguous	1.32	Destabilizing	0.622	Likely Pathogenic	-2.58	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.52	Pathogenic	0.01	Affected	3.38	19	0.0579	0.2145		1	2	-2.6	18.03
c.806T>A	I269K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I269K is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools largely agree on a deleterious effect: SIFT is the sole benign predictor, whereas the remaining methods—SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates pathogenicity, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. FoldX and Rosetta individually report uncertain effects, and Foldetta remains unavailable. Overall, the consensus of the majority of evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.216401	Structured	0.343787	Uncertain	0.937	0.244	0.125											-14.609	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	1.45	Ambiguous	0.1	1.86	Ambiguous	1.66	Ambiguous	1.55	Destabilizing	0.763	Likely Pathogenic	-5.10	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.76	Pathogenic	0.06	Tolerated			0.0878	0.0713		-2	-3	-8.4	15.01
c.806T>G	I269R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I269R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: the benign group contains only SIFT, whereas the pathogenic group includes SGM‑Consensus (Likely Pathogenic), REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX and Rosetta give uncertain results, and Foldetta is also uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta as unavailable. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.216401	Structured	0.343787	Uncertain	0.937	0.244	0.125											-14.567	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	1.34	Ambiguous	0.1	1.99	Ambiguous	1.67	Ambiguous	1.50	Destabilizing	0.765	Likely Pathogenic	-5.23	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.69	Pathogenic	0.07	Tolerated			0.1108	0.0870		-2	-3	-9.0	43.03
c.807A>G	I269M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I269M is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include PROVEAN and AlphaMissense‑Optimized, whereas REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default predict it to be pathogenic. Five tools (FoldX, Rosetta, Foldetta, premPS, and ESM1b) give uncertain results. High‑accuracy methods give mixed evidence: AlphaMissense‑Optimized reports a benign effect, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenicity, and Foldetta remains uncertain. Overall, the majority of predictions support a pathogenic impact, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.216401	Structured	0.343787	Uncertain	0.937	0.244	0.125											-7.863	In-Between	0.715	Likely Pathogenic	Likely Benign	0.91	Ambiguous	0.1	1.66	Ambiguous	1.29	Ambiguous	0.94	Ambiguous	0.507	Likely Pathogenic	-2.19	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	1.75	Pathogenic	0.05	Affected			0.0580	0.2283		2	1	-2.6	18.03
c.809A>T	E270V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E270V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that assess sequence conservation and structural impact uniformly classify the substitution as pathogenic: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return pathogenic scores. No tool predicts a benign effect. Uncertain results are reported only by FoldX, Rosetta, Foldetta, and premPS, which are not considered evidence for or against pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic”; Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, is inconclusive. Overall, the consensus of available predictions indicates that E270V is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.144935	Structured	0.382573	Uncertain	0.938	0.231	0.125											-15.969	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	1.38	Ambiguous	0.6	1.88	Ambiguous	1.63	Ambiguous	-0.52	Ambiguous	0.574	Likely Pathogenic	-6.43	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.53	Pathogenic	0.00	Affected			0.0672	0.4498		-2	-2	7.7	-29.98
c.814C>T	R272W 2D AISynGAP1 missense variant R272W is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a predominance of pathogenic calls: FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict deleterious effects, while the consensus SGM tool (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports a likely pathogenic outcome. Benign predictions are limited to REVEL, Rosetta, and premPS. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is inconclusive, whereas Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. Overall, the balance of evidence favors a pathogenic impact for R272W, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.071867	Structured	0.425620	Uncertain	0.925	0.215	0.125											-12.145	Likely Pathogenic	0.863	Likely Pathogenic	Ambiguous	2.98	Destabilizing	1.6	0.12	Likely Benign	1.55	Ambiguous	0.19	Likely Benign	0.461	Likely Benign	-5.49	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.72	Pathogenic	0.00	Affected			0.1460	0.3643		2	-3	3.6	30.03
c.823C>G	P275A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P275A is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33437728‑C‑G). Prediction tools that agree on a benign effect include REVEL, premPS, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments are less decisive: AlphaMissense‑Optimized reports a benign outcome, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta is uncertain. Consequently, the overall evidence leans toward a benign interpretation, with no ClinVar record to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.059222	Structured	0.353469	Uncertain	0.811	0.208	0.250								6-33437728-C-G	1	6.20e-7	-6.137	Likely Benign	0.133	Likely Benign	Likely Benign	1.87	Ambiguous	0.2	1.11	Ambiguous	1.49	Ambiguous	0.50	Likely Benign	0.410	Likely Benign	-4.95	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.79	Pathogenic	0.32	Tolerated	3.38	19	0.3475	0.3243		-1	1	3.4	-26.04
c.829A>C	K277Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K277Q is reported in gnomAD (ID 6‑33437734‑A‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions from FoldX, Foldetta, and premPS; pathogenic predictions from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: Rosetta and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evidence points toward a pathogenic effect, with only a minority of tools indicating benign or uncertain outcomes. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.061840	Structured	0.321811	Uncertain	0.649	0.247	0.250								6-33437734-A-C	1	6.20e-7	-12.547	Likely Pathogenic	0.904	Likely Pathogenic	Ambiguous	0.03	Likely Benign	0.1	0.63	Ambiguous	0.33	Likely Benign	0.42	Likely Benign	0.655	Likely Pathogenic	-3.68	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.83	Pathogenic	0.02	Affected	3.38	19	0.4000	0.0672		1	1	0.4	-0.04
c.830A>C	K277T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K277T missense variant is not reported in ClinVar (status: None) and has no entry in gnomAD. Prediction tools that agree on a benign effect are Rosetta and premPS, while the remaining tools—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict pathogenicity. FoldX and Foldetta return uncertain results. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also pathogenic; Foldetta remains uncertain. Overall, the preponderance of evidence indicates that K277T is most likely pathogenic, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.061840	Structured	0.321811	Uncertain	0.649	0.247	0.250											-11.688	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic	1.46	Ambiguous	0.1	0.14	Likely Benign	0.80	Ambiguous	0.17	Likely Benign	0.573	Likely Pathogenic	-5.52	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.02	Pathogenic	0.01	Affected			0.1837	0.2220		0	-1	3.2	-27.07
c.831G>C	K277N 2D AIThe SynGAP1 missense variant K277N is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, and premPS. Tools that predict pathogenicity are SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, SGM‑Consensus as Likely Pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as Benign. No predictions are missing or inconclusive. Overall, the majority of tools (10/14) predict pathogenicity, whereas four tools predict benign. Therefore, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.061840	Structured	0.321811	Uncertain	0.649	0.247	0.250											-9.646	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	-0.07	Likely Benign	0.4	0.08	Likely Benign	0.01	Likely Benign	0.46	Likely Benign	0.572	Likely Pathogenic	-4.60	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.83	Pathogenic	0.03	Affected			0.3265	0.0568		1	0	0.4	-14.07
c.831G>T	K277N 2D AIThe SynGAP1 missense variant K277N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include FoldX, Rosetta, Foldetta, and premPS. In contrast, the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is also likely pathogenic; Foldetta, a protein‑folding stability predictor, reports a benign effect. Overall, the preponderance of evidence (10 pathogenic vs. 4 benign predictions) points to a pathogenic classification. This conclusion is not contradicted by ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.061840	Structured	0.321811	Uncertain	0.649	0.247	0.250											-9.646	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	-0.07	Likely Benign	0.4	0.08	Likely Benign	0.01	Likely Benign	0.46	Likely Benign	0.572	Likely Pathogenic	-4.60	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.83	Pathogenic	0.03	Affected			0.3265	0.0568		1	0	0.4	-14.07
c.832A>C	K278Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K278Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, and Foldetta. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: premPS and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts a likely pathogenic outcome, whereas Foldetta (combining FoldX‑MD and Rosetta stability outputs) predicts a benign effect, and AlphaMissense‑Optimized remains uncertain. Overall, the majority of evidence points to a pathogenic impact for K278Q, and this conclusion does not contradict the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.120615	Structured	0.310130	Uncertain	0.748	0.253	0.125											-11.107	Likely Pathogenic	0.902	Likely Pathogenic	Ambiguous	0.23	Likely Benign	0.1	0.25	Likely Benign	0.24	Likely Benign	0.73	Ambiguous	0.387	Likely Benign	-3.63	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.71	Pathogenic	0.05	Affected			0.3770	0.0672		1	1	0.4	-0.04
c.833A>C	K278T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K278T is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, Rosetta, Foldetta, and premPS. Tools that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; FoldX is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as benign. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict any ClinVar annotation because the variant is not yet classified in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.120615	Structured	0.310130	Uncertain	0.748	0.253	0.125											-11.227	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.85	Ambiguous	0.2	-0.08	Likely Benign	0.39	Likely Benign	0.46	Likely Benign	0.484	Likely Benign	-5.40	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.70	Pathogenic	0.04	Affected			0.1775	0.2220		0	-1	3.2	-27.07
c.834G>C	K278N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K278N is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, Rosetta, premPS, and SIFT, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy methods give mixed results: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) predicts benign. Overall, the majority of tools support a pathogenic effect, so the variant is most likely pathogenic; this is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.120615	Structured	0.310130	Uncertain	0.748	0.253	0.125											-10.611	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.40	Likely Benign	0.0	0.05	Likely Benign	0.23	Likely Benign	0.44	Likely Benign	0.255	Likely Benign	-4.51	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.81	Pathogenic	0.07	Tolerated			0.3071	0.0568		1	0	0.4	-14.07
c.834G>T	K278N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K278N is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, premPS, and SIFT, whereas tools that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. With a majority of evidence pointing to deleterious effects and no ClinVar annotation to contradict, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.120615	Structured	0.310130	Uncertain	0.748	0.253	0.125											-10.611	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.40	Likely Benign	0.0	0.05	Likely Benign	0.23	Likely Benign	0.44	Likely Benign	0.255	Likely Benign	-4.51	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.81	Pathogenic	0.07	Tolerated			0.3071	0.0568		1	0	0.4	-14.07
c.835C>T	R279W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R279W is listed in ClinVar with an uncertain significance (ClinVar ID 1204186.0) and is not reported in gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining pathogenic‑predicating tools—FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—consistently predict a deleterious impact. Uncertain or inconclusive results come from Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for R279W, which contrasts with the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.155435	Structured	0.309382	Uncertain	0.887	0.257	0.125					Uncertain		1				-11.417	Likely Pathogenic	0.942	Likely Pathogenic	Ambiguous	2.00	Destabilizing	0.8	1.47	Ambiguous	1.74	Ambiguous	0.80	Ambiguous	0.485	Likely Benign	-6.29	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.88	Pathogenic	0.00	Affected	3.39	18	0.1200	0.2519		2	-3	3.6	30.03	270.0	38.3	0.1	0.0	0.3	0.0								Uncertain	The guanidinium group of Arg279, located at the beginning of an anti-parallel β sheet strand (res. Arg279-Leu286), can form hydrogen bond with the backbone carbonyl groups of nearby loop residues (e.g., Ser296, Ser331, and As332) and form salt bridges with the carboxylate groups of Asp330 and Asp332. In the WT simulations, Arg279 sporadically forms a salt bridge even with the carboxylate group of Glu613, loosely connecting the C2 domain and GAP domain. Meanwhile, the indole ring of the Trp279 side chain is unable to hydrogen bond with the loop residues in the variant simulations. The lack of hydrogen bond or salt bridge formation with the loop residues could be significant, as Arg279 and the loops face the polar head group region of the membrane. Thus, although Trp279 could interact with the membrane surface as a “lipid anchor,” any changes to the wider loop dynamics could still adversely affect the formation of a stable SynGAP-membrane association. However, no definite conclusions on the effect of the residue swap on the SynGAP-membrane association can be drawn from solvent-only simulations.
c.839A>C	Y280S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y280S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect. Benign predictions are absent; all evaluated algorithms (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) classify the substitution as pathogenic. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a likely pathogenic verdict, and Foldetta (integrating FoldX‑MD and Rosetta outputs) also reports pathogenic. Consequently, the variant is most likely pathogenic, and this prediction is consistent with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.161087	Structured	0.321243	Uncertain	0.917	0.248	0.125											-13.491	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	4.63	Destabilizing	0.3	4.80	Destabilizing	4.72	Destabilizing	2.03	Destabilizing	0.635	Likely Pathogenic	-8.27	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.00	Pathogenic	0.05	Affected			0.3993	0.1227		-3	-2	0.5	-76.10
c.842A>C	Y281S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y281S is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools cluster into two groups: the single benign prediction comes from SIFT, while the remaining tools—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—predict pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is Pathogenic. With the overwhelming majority of evidence indicating pathogenicity and no ClinVar annotation to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.337647	Uncertain	0.927	0.254	0.000											-9.541	Likely Pathogenic	0.847	Likely Pathogenic	Ambiguous	3.24	Destabilizing	0.3	3.02	Destabilizing	3.13	Destabilizing	1.59	Destabilizing	0.642	Likely Pathogenic	-5.68	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.02	Pathogenic	0.12	Tolerated			0.4203	0.2543		-3	-2	0.5	-76.10
c.844T>C	C282R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C282R is listed in ClinVar as Pathogenic (ClinVar ID 635755.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect are limited to REVEL, which scores the variant as benign. All other evaluated algorithms predict a pathogenic outcome: FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Rosetta’s output is uncertain and is therefore not counted as evidence. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) also predicts pathogenic. Based on the overwhelming agreement among these predictions, the variant is most likely pathogenic, which aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.348535	Uncertain	0.942	0.250	0.000					Pathogenic		2				-16.378	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.13	Destabilizing	0.6	1.58	Ambiguous	2.36	Destabilizing	1.70	Destabilizing	0.466	Likely Benign	-11.03	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.63	Pathogenic	0.00	Affected	3.39	18	0.1696	0.1557		-4	-3	-7.0	53.05	297.4	-98.2	-0.1	0.1	0.5	0.0	X		X				X	Potentially Pathogenic	The thiol-containing side chain of Cys282, located at the beginning of an anti-parallel β sheet strand (res. Arg279-Leu286), is packed against multiple hydrophobic residues (e.g., Ile268, Leu284, Trp308, Leu327). In the variant simulations, the bulky side chain of Arg282 with its positively charged guanidinium group is not suitable for this hydrophobic niche. Consequently, the hydrophobic residues must either make room to accommodate Arg282 or it must escape the hydrophobic C2 domain core.As a result, new hydrogen bonds are formed with the backbone carbonyl groups of the surrounding β sheet residues Ala399, Leu325, and His326, which decreases the unity of the secondary structure elements. Notably, it is likely that the residue swap causes major problems during the C2 domain folding that are not visible in the variant simulations. In fact, even increased lability in the C2 domain could adversely affect the establishment of a stable SynGAP-membrane association.
c.845G>A	C282Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C282Y resides in the C2 domain. ClinVar has no entry for this variant, and it is not listed in gnomAD. Prediction tools that indicate a benign effect are REVEL and premPS. All other evaluated algorithms—FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.348535	Uncertain	0.942	0.250	0.000											-13.438	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	8.50	Destabilizing	1.1	2.91	Destabilizing	5.71	Destabilizing	0.41	Likely Benign	0.419	Likely Benign	-10.11	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.63	Pathogenic	0.00	Affected			0.1069	0.3089		0	-2	-3.8	60.04
c.845G>T	C282F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C282F is not listed in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions are provided by REVEL and premPS, whereas the remaining 13 tools (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all indicate pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports a pathogenic outcome. Taken together, the overwhelming majority of evidence points to a pathogenic impact for C282F. This conclusion is consistent with the absence of a ClinVar entry, which does not contradict the prediction. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.348535	Uncertain	0.942	0.250	0.000											-13.288	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	6.22	Destabilizing	1.4	2.38	Destabilizing	4.30	Destabilizing	0.42	Likely Benign	0.430	Likely Benign	-10.11	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.65	Pathogenic	0.00	Affected			0.1267	0.3607		-4	-2	0.3	44.04
c.846T>G	C282W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change C282W is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are limited to REVEL, which scores the variant as benign. All other evaluated predictors—FoldX, Foldetta, SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. Uncertain results come only from premPS and Rosetta, which are treated as unavailable. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports a likely pathogenic status; and Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, also predicts pathogenic. **Thus, the variant is most likely pathogenic based on the collective predictions, and this conclusion is not contradicted by any ClinVar annotation.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.348535	Uncertain	0.942	0.250	0.000											-15.392	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	10.69	Destabilizing	1.7	-1.05	Ambiguous	4.82	Destabilizing	0.70	Ambiguous	0.418	Likely Benign	-10.11	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.63	Pathogenic	0.03	Affected			0.1457	0.2978		-8	-2	-3.4	83.07
c.848A>T	E283V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E283V missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are FoldX and premPS, while the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools give inconclusive results: Rosetta (Uncertain) and Foldetta (Uncertain). High‑accuracy methods specifically indicate that AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as likely pathogenic, whereas Foldetta’s stability assessment is uncertain. Taken together, the preponderance of evidence from both general and high‑accuracy predictors points to a pathogenic effect for E283V. This conclusion is consistent with the absence of ClinVar annotation and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.358602	Uncertain	0.950	0.249	0.000											-13.602	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.44	Likely Benign	0.2	0.56	Ambiguous	0.50	Ambiguous	0.36	Likely Benign	0.558	Likely Pathogenic	-6.43	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.83	Pathogenic	0.00	Affected			0.0874	0.6011		-2	-2	7.7	-29.98
c.850C>T	L284F 2D AIThe SynGAP1 missense variant L284F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while Rosetta, Foldetta, and premPS are inconclusive. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains uncertain. Taken together, the overwhelming majority of evidence indicates that the variant is most likely pathogenic, and this conclusion is consistent with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.094817	Structured	0.371601	Uncertain	0.950	0.255	0.000											-11.656	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	2.04	Destabilizing	1.9	1.05	Ambiguous	1.55	Ambiguous	0.62	Ambiguous	0.654	Likely Pathogenic	-3.51	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.69	Pathogenic	0.01	Affected			0.0515	0.2779		2	0	-1.0	34.02
c.853T>C	C285R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C285R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FoldX, which scores the variant as benign. All other evaluated predictors—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus confirms a likely pathogenic status, while Foldetta (combining FoldX‑MD and Rosetta outputs) remains uncertain. Consequently, the preponderance of evidence points to a pathogenic effect for C285R, and this conclusion does not contradict any existing ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.144935	Structured	0.375400	Uncertain	0.946	0.250	0.000											-9.127	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic	-0.47	Likely Benign	0.2	-0.63	Ambiguous	-0.55	Ambiguous	1.53	Destabilizing	0.583	Likely Pathogenic	-9.66	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.83	Pathogenic	0.04	Affected			0.1947	0.1453		-4	-3	-7.0	53.05
c.854G>A	C285Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C285Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and Rosetta. Those that agree on a pathogenic effect include SGM‑Consensus, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. Predictions that are inconclusive are Foldetta, premPS, ESM1b, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic impact for C285Y. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.144935	Structured	0.375400	Uncertain	0.946	0.250	0.000											-7.210	In-Between	0.895	Likely Pathogenic	Ambiguous	3.66	Destabilizing	1.1	-2.33	Stabilizing	0.67	Ambiguous	0.53	Ambiguous	0.484	Likely Benign	-8.67	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.88	Pathogenic	0.18	Tolerated			0.1413	0.3689		0	-2	-3.8	60.04
c.854G>T	C285F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C285F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include premPS, SIFT, and AlphaMissense‑Optimized, whereas a majority of tools (SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic outcome; Foldetta is uncertain. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence (12 pathogenic vs. 3 benign predictions) indicates that the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.144935	Structured	0.375400	Uncertain	0.946	0.250	0.000											-9.397	Likely Pathogenic	0.716	Likely Pathogenic	Likely Benign	3.27	Destabilizing	1.1	-1.72	Ambiguous	0.78	Ambiguous	0.35	Likely Benign	0.500	Likely Pathogenic	-8.84	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.81	Pathogenic	0.12	Tolerated			0.1626	0.4007		-4	-2	0.3	44.04
c.855C>G	C285W 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant C285W is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and Rosetta, whereas pathogenic predictions are made by SGM‑Consensus, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy subset confirms this trend: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates pathogenicity, and Foldetta remains uncertain. No prediction tool is missing or inconclusive enough to alter the overall assessment. Consequently, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.144935	Structured	0.375400	Uncertain	0.946	0.250	0.000											-9.017	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic	3.35	Destabilizing	1.1	-2.28	Stabilizing	0.54	Ambiguous	0.61	Ambiguous	0.327	Likely Benign	-8.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.78	Pathogenic	0.11	Tolerated			0.1934	0.3697		-8	-2	-3.4	83.07
c.860A>C	D287A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D287A is listed in ClinVar with an Uncertain significance status and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, FoldX, Rosetta, Foldetta, and premPS, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (integrating FoldX‑MD and Rosetta) as benign. The overall tally favors pathogenicity (8 tools vs 5 benign), but the conflicting high‑accuracy results leave uncertainty. Thus, the variant is most likely pathogenic according to the majority of predictions, which does not contradict its ClinVar Uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.102787	Structured	0.389029	Uncertain	0.912	0.268	0.000					Uncertain		1				-14.686	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.30	Likely Benign	0.1	-0.04	Likely Benign	0.13	Likely Benign	0.40	Likely Benign	0.484	Likely Benign	-7.35	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.58	Pathogenic	0.01	Affected	3.38	23	0.4448	0.7431		-2	0	5.3	-44.01
c.863A>C	D288A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D288A missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, and SIFT. Those that agree on a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized, Foldetta, and Rosetta give uncertain results and are treated as unavailable for pathogenicity inference. High‑accuracy assessments show that the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenicity, AlphaMissense‑Optimized is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also uncertain. Overall, seven tools predict pathogenicity while four predict benign, with no conflicting ClinVar evidence. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.125101	Structured	0.395525	Uncertain	0.873	0.261	0.000											-13.470	Likely Pathogenic	0.908	Likely Pathogenic	Ambiguous	0.34	Likely Benign	0.1	1.27	Ambiguous	0.81	Ambiguous	0.10	Likely Benign	0.451	Likely Benign	-6.09	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.71	Pathogenic	0.07	Tolerated			0.4060	0.5788		0	-2	5.3	-44.01
c.872A>C	Y291S 2D AIThe SynGAP1 missense variant Y291S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). All evaluated in silico predictors classify the variant as pathogenic: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No predictions or stability results are missing or inconclusive. Based on the unanimous pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.173081	Structured	0.383842	Uncertain	0.912	0.251	0.000											-11.928	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	3.47	Destabilizing	0.8	4.47	Destabilizing	3.97	Destabilizing	2.01	Destabilizing	0.588	Likely Pathogenic	-7.31	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.83	Pathogenic	0.02	Affected			0.4850	0.2079		-3	-2	0.5	-76.10
c.875C>A	A292E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A292E is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, whereas the remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support this view: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it likely pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for A292E. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.247041	Structured	0.362042	Uncertain	0.929	0.256	0.000											-14.282	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	6.07	Destabilizing	1.2	3.82	Destabilizing	4.95	Destabilizing	1.54	Destabilizing	0.475	Likely Benign	-4.60	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.69	Pathogenic	0.02	Affected			0.1444	0.2205		0	-1	-5.3	58.04
c.877C>T	R293C 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R293C is listed in ClinVar with an uncertain significance (ClinVar ID 2500611.0) and is present in gnomAD (6‑33437782‑C‑T). Prediction tools that classify the variant as benign include premPS, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict it to be pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result. Consequently, the overwhelming majority of computational evidence indicates a pathogenic impact for R293C. This prediction aligns with the ClinVar designation of uncertain significance, not contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.335645	Structured	0.338192	Uncertain	0.924	0.269	0.125					Uncertain		1	6-33437782-C-T	3	1.86e-6	-12.844	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	1.38	Ambiguous	0.1	0.62	Ambiguous	1.00	Ambiguous	0.02	Likely Benign	0.579	Likely Pathogenic	-7.35	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.46	Pathogenic	0.00	Affected	3.38	23	0.3031	0.4363		-4	-3	7.0	-53.05	226.0	96.5	0.0	0.0	0.1	0.1		X		X			X	Potentially Pathogenic	The guanidinium group of the Arg293 side chain, located in an anti-parallel β sheet strand (res. Met289-Pro298), packs against the phenol ring of the Tyr281 side chain or forms a salt bridge with the carboxylate group of Glu283 on the outer side of the C2 domain. The positively charged guanidinium side chain of arginine is on the outside surface of the hydrophobic C2 domain, resulting in a twist in the β strand. Although this twist is maintained in the variant simulations, replacing the positively charged residue with a more hydrophobic one, such as cysteine, could remove the twist during protein folding.Because Arg293 is positioned at the C2 and PH domain interface, the residue swap could significantly impact the tertiary structure assembly. Notably, Arg293 is located at the SynGAP-Ras interface, and its role in complex formation cannot be fully understood through solvent-only simulations.
c.878G>A	R293H 2D AISynGAP1 missense variant R293H is listed in ClinVar with an uncertain significance (ClinVar ID 3901513.0) and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL and premPS, whereas the remaining 13 tools—FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, classifies the variant as pathogenic. Overall, the preponderance of evidence indicates that R293H is most likely pathogenic, a conclusion that does not contradict the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.335645	Structured	0.338192	Uncertain	0.924	0.269	0.125					Uncertain		1				-13.009	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	4.45	Destabilizing	2.3	2.12	Destabilizing	3.29	Destabilizing	0.32	Likely Benign	0.438	Likely Benign	-4.60	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.45	Pathogenic	0.04	Affected			0.3120	0.2573		2	0	1.3	-19.05
c.880A>C	T294P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T294P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX (Uncertain), Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. No tool reports a benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is pathogenic; SGM‑Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.316932	Uncertain	0.919	0.267	0.125											-17.477	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	1.97	Ambiguous	0.3	5.18	Destabilizing	3.58	Destabilizing	1.15	Destabilizing	0.741	Likely Pathogenic	-5.52	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-0.19	Pathogenic	0.01	Affected			0.1906	0.4479		0	-1	-0.9	-3.99
c.881C>A	T294N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T294N is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess functional impact uniformly classify the variant as pathogenic: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy methods reinforce this assessment: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts pathogenic. Based on the unanimous pathogenic predictions and the absence of any benign calls, the variant is most likely pathogenic, and this conclusion does not contradict the current ClinVar status (no report). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.316932	Uncertain	0.919	0.267	0.125											-14.925	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	2.74	Destabilizing	0.2	2.66	Destabilizing	2.70	Destabilizing	1.56	Destabilizing	0.630	Likely Pathogenic	-4.60	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-0.18	Pathogenic	0.01	Affected			0.1040	0.3239		0	0	-2.8	13.00
c.881C>T	T294I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T294I is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on pathogenicity include REVEL, FoldX, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools with uncertain or inconclusive results are Rosetta and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Based on the overwhelming agreement among pathogenic predictions and the high‑accuracy tool results, the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.316932	Uncertain	0.919	0.267	0.125											-15.302	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	4.09	Destabilizing	0.2	1.33	Ambiguous	2.71	Destabilizing	0.54	Ambiguous	0.768	Likely Pathogenic	-5.52	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-0.19	Pathogenic	0.01	Affected			0.0808	0.5485		0	-1	5.2	12.05
c.883A>C	T295P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T295P is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include FoldX and AlphaMissense‑Optimized, whereas the remaining evaluated algorithms (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) all predict a pathogenic outcome. High‑accuracy assessments further show that AlphaMissense‑Optimized classifies the variant as benign, the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it as likely pathogenic, and Foldetta reports an uncertain stability change. With the majority of evidence pointing to deleterious effects, the variant is most likely pathogenic, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.401658	Structured	0.295548	Uncertain	0.881	0.288	0.125											-9.941	Likely Pathogenic	0.688	Likely Pathogenic	Likely Benign	0.26	Likely Benign	0.2	3.30	Destabilizing	1.78	Ambiguous	0.60	Ambiguous	0.531	Likely Pathogenic	-4.65	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.90	Pathogenic	0.02	Affected			0.2442	0.5327		0	-1	-0.9	-3.99
c.884C>A	T295N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T295N missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, ESM1b, and Foldetta, while those that predict a pathogenic outcome are SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, seven tools predict pathogenicity versus four predicting benign, with no ClinVar evidence to contradict this assessment. Thus, the variant is most likely pathogenic based on the available predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.401658	Structured	0.295548	Uncertain	0.881	0.288	0.125											-6.588	Likely Benign	0.793	Likely Pathogenic	Ambiguous	0.24	Likely Benign	0.1	0.66	Ambiguous	0.45	Likely Benign	0.89	Ambiguous	0.438	Likely Benign	-3.51	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.93	Pathogenic	0.03	Affected			0.1522	0.4457		0	0	-2.8	13.00
c.884C>T	T295I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant T295I is reported in gnomAD (ID 6‑33437789‑C‑T) but has no ClinVar entry. Functional prediction tools cluster into two consensus groups: benign predictions come from FoldX and Foldetta, while pathogenic predictions are supported by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain results are reported by AlphaMissense‑Optimized, Rosetta, and premPS and are treated as inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (integrating FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evidence points toward a pathogenic effect, with only a minority of tools indicating benign or uncertain outcomes. This prediction does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.401658	Structured	0.295548	Uncertain	0.881	0.288	0.125								6-33437789-C-T	4	2.48e-6	-9.330	Likely Pathogenic	0.892	Likely Pathogenic	Ambiguous	0.21	Likely Benign	0.2	0.55	Ambiguous	0.38	Likely Benign	0.58	Ambiguous	0.607	Likely Pathogenic	-4.87	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.88	Pathogenic	0.04	Affected	3.38	23	0.1025	0.5599		-1	0	5.2	12.05
c.887C>A	S296Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S296Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, and premPS, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX and Foldetta give uncertain results. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic, and Foldetta remains uncertain. Overall, the majority of evidence points to a pathogenic impact. The variant is most likely pathogenic based on predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.444081	Structured	0.282669	Uncertain	0.887	0.284	0.250											-12.148	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.46	Ambiguous	0.2	0.48	Likely Benign	0.97	Ambiguous	0.15	Likely Benign	0.486	Likely Benign	-4.34	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.93	Pathogenic	0.05	Affected			0.0800	0.5610		-3	-2	-0.5	76.10
c.887C>G	S296C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S296C is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as benign. No predictions or stability results are missing or inconclusive. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.444081	Structured	0.282669	Uncertain	0.887	0.284	0.250											-7.842	In-Between	0.286	Likely Benign	Likely Benign	0.46	Likely Benign	0.1	-0.11	Likely Benign	0.18	Likely Benign	0.09	Likely Benign	0.361	Likely Benign	-1.46	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	1.91	Pathogenic	0.05	Affected			0.1052	0.6052		0	-1	3.3	16.06
c.887C>T	S296F 2D AIThe SynGAP1 missense variant S296F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, and premPS. In contrast, the majority of tools predict a pathogenic impact: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic; SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive and therefore unavailable as evidence. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant has not been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.444081	Structured	0.282669	Uncertain	0.887	0.284	0.250											-11.721	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	1.29	Ambiguous	1.6	0.24	Likely Benign	0.77	Ambiguous	0.29	Likely Benign	0.494	Likely Benign	-4.34	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.94	Pathogenic	0.04	Affected			0.0720	0.5905		-3	-2	3.6	60.10
c.889A>C	K297Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K297Q missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include REVEL, Rosetta, and Foldetta. In contrast, the majority of tools predict a pathogenic outcome: SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX is uncertain and is treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as benign. Overall, the preponderance of evidence points to a pathogenic effect for K297Q. This conclusion is not contradicted by ClinVar status, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.422041	Structured	0.272593	Uncertain	0.880	0.285	0.375											-8.393	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	0.66	Ambiguous	0.3	0.14	Likely Benign	0.40	Likely Benign	1.06	Destabilizing	0.450	Likely Benign	-3.48	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.65	Pathogenic	0.01	Affected			0.4768	0.1738		1	1	0.4	-0.04
c.890A>C	K297T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K297T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are none, whereas those that predict a pathogenic effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain predictions come from FoldX, Rosetta, Foldetta, and premPS. High‑accuracy methods specifically show AlphaMissense‑Optimized as pathogenic, SGM Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.422041	Structured	0.272593	Uncertain	0.880	0.285	0.375											-10.110	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	1.55	Ambiguous	0.1	1.19	Ambiguous	1.37	Ambiguous	0.59	Ambiguous	0.551	Likely Pathogenic	-5.28	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.62	Pathogenic	0.01	Affected			0.2294	0.4024		0	-1	3.2	-27.07
c.891G>C	K297N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K297N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic impact. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results and are therefore not considered evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.422041	Structured	0.272593	Uncertain	0.880	0.285	0.375											-11.328	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.08	Ambiguous	0.1	1.60	Ambiguous	1.34	Ambiguous	1.15	Destabilizing	0.253	Likely Benign	-4.31	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.61	Pathogenic	0.01	Affected			0.3797	0.2265		1	0	0.4	-14.07
c.891G>T	K297N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K297N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic impact. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results and are therefore not considered evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the preponderance of pathogenic predictions and the lack of benign consensus, K297N is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.422041	Structured	0.272593	Uncertain	0.880	0.285	0.375											-11.328	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.08	Ambiguous	0.1	1.60	Ambiguous	1.34	Ambiguous	1.15	Destabilizing	0.253	Likely Benign	-4.31	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.61	Pathogenic	0.01	Affected			0.3797	0.2265		1	0	0.4	-14.07
c.895C>T	R299C 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R299C is listed in ClinVar with an uncertain significance (ClinVar ID 1335623.0) and is present in gnomAD (ID 6‑33437800‑C‑T). Prediction tools that classify the variant as benign include REVEL, SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as likely pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Other stability predictors (FoldX, Rosetta, premPS) are also uncertain. Overall, the balance of evidence favors a pathogenic interpretation, which does not contradict the ClinVar uncertain status but suggests a higher likelihood of disease relevance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.262979	Uncertain	0.819	0.295	0.500					Conflicting		2	6-33437800-C-T	3	1.86e-6	-6.326	Likely Benign	0.572	Likely Pathogenic	Likely Benign	1.85	Ambiguous	0.4	0.61	Ambiguous	1.23	Ambiguous	0.76	Ambiguous	0.344	Likely Benign	-3.54	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.65	Pathogenic	0.06	Tolerated	3.39	19	0.3035	0.4564		-4	-3	7.0	-53.05	210.7	91.3	0.1	0.0	0.0	0.2	X	X						Potentially Pathogenic	The guanidinium group of Arg299, located in a β hairpin loop linking two anti-parallel β sheet strands (res. Met289-Pro298, res. Thr305-Asn315), forms hydrogen bonds that stabilize the tight turn. In the WT simulations, the Arg299 side chain hydrogen bonds with the loop backbone carbonyl groups (e.g., Ser302, Thr305, Leu274, Gly303), the hydroxyl group of Ser300, and even forms a salt bridge with the carboxylate group of Asp304.In the variant simulations, the thiol group of the Cys299 side chain is unable to form any of these well-coordinated or strong interactions, which could affect the initial formation of the secondary hairpin loop during folding. β hairpins are potential nucleation sites during the initial stages of protein folding, so even minor changes in them could be significant. Moreover, the positively charged Arg299 side chain faces the polar head group region of the inner leaflet membrane and could directly anchor the C2 domain to the membrane. In short, the residue swap could negatively affect both protein folding and the stability of the SynGAP-membrane association.
c.896G>A	R299H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R299H is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33437801‑G‑A). Functional prediction tools cluster into two groups: benign predictions from REVEL and AlphaMissense‑Optimized, and pathogenic predictions from FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; Rosetta, ESM1b, and AlphaMissense‑Default are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as pathogenic, and the SGM consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a tie between pathogenic and uncertain calls. Overall, the majority of evidence points to a pathogenic effect, which is consistent with the ClinVar uncertain designation rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.321458	Structured	0.262979	Uncertain	0.819	0.295	0.500					Conflicting		2	6-33437801-G-A	10	6.20e-6	-7.731	In-Between	0.388	Ambiguous	Likely Benign	3.97	Destabilizing	1.0	0.94	Ambiguous	2.46	Destabilizing	1.41	Destabilizing	0.238	Likely Benign	-3.35	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.69	Pathogenic	0.02	Affected	3.39	19	0.3293	0.2982		2	0	1.3	-19.05	211.2	72.5	-0.1	0.2	-0.2	0.3	X							Potentially Pathogenic	The guanidinium group of Arg299, located in a β hairpin loop linking two anti-parallel β sheet strands (res. Met289-Pro298, res. Thr305-Asn315), forms hydrogen bonds that stabilize the tight turn. In the WT simulations, the Arg299 side chain hydrogen bonds with the loop backbone carbonyl groups (e.g., Ser302, Thr305, Leu274, Gly303), the hydroxyl group of Ser300, and even forms a salt bridge with the carboxylate group of Asp304.In the variant simulations, the imidazole ring of His299 (epsilon protonated state) hydrogen bonds with the carbonyl group of Asp304 and the hydroxyl group of Ser300. However, it does not form as many or as strong interactions as arginine, which could affect the initial formation of the secondary hairpin loop during folding. β hairpins are potential nucleation sites during the initial stages of protein folding, so even minor changes in them could be significant.Additionally, His299 prefers to hydrophobically interact with other hydrophobic residues inside the C2 domain core (e.g., Val306, Leu274), which destabilizes the C2 domain. Indeed, the β strand partially unfolds during the second simulation. Moreover, the positively charged Arg299 side chain faces the polar head group region of the inner leaflet membrane and could directly anchor the C2 domain to the membrane. In short, the residue swap could negatively affect both protein folding and the stability of the SynGAP-membrane association.
c.911A>C	D304A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D304A variant has no ClinVar entry and is not listed in gnomAD. Prediction tools that classify it as benign include premPS, ESM1b, and AlphaMissense‑Optimized, whereas the remaining tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) all predict a pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of evidence points to a pathogenic impact. This prediction does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.352862	Structured	0.285053	Uncertain	0.764	0.271	0.250											-6.258	Likely Benign	0.604	Likely Pathogenic	Likely Benign	1.00	Ambiguous	0.1	0.54	Ambiguous	0.77	Ambiguous	0.39	Likely Benign	0.523	Likely Pathogenic	-5.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.80	Pathogenic	0.02	Affected			0.4457	0.6642		0	-2	5.3	-44.01
c.920T>G	F307C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F307C missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). In silico predictors overwhelmingly indicate a deleterious effect: all tools that provide a definitive call—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The only predictions that are inconclusive are FoldX, Rosetta, and Foldetta, which are treated as unavailable. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely pathogenic status; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains uncertain. **Based on the consensus of the available predictions, the variant is most likely pathogenic, and this assessment is not contradicted by any ClinVar status.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.298791	Structured	0.327302	Uncertain	0.900	0.315	0.125											-11.484	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	1.36	Ambiguous	0.1	1.44	Ambiguous	1.40	Ambiguous	1.05	Destabilizing	0.754	Likely Pathogenic	-7.35	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.92	Pathogenic	0.00	Affected			0.2729	0.1628		-4	-2	-0.3	-44.04